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  1. Anemia in Chronic Kidney Disease

    MedlinePlus

    ... Heart Disease Mineral & Bone Disorder Anemia in Chronic Kidney Disease What is anemia? Anemia is a condition ... they should. How is anemia related to chronic kidney disease? Anemia commonly occurs in people with chronic ...

  2. Anemia in thyroid diseases.

    PubMed

    Szczepanek-Parulska, Ewelina; Hernik, Aleksandra; Ruchała, Marek

    2017-03-28

    Anemia is a frequent, although often underestimated, clinical condition accompanying thyroid diseases. In spite of the fact that anemia and thyroid dysfunction often occur simultaneously, the causative relationship between these two disorders remains ambiguous. Thyroid hormones stimulate erythrocytes precursors proliferation directly, as well as via erythropoietin production enhancement, whereas iron-deficient anemia negatively influences thyroid hormonal status. Thus, different forms of anemia might emerge in the course of thyroid dysfunction. In fact, normocytic anemia is most common, while macrocytic or microcytic anemia occur less frequently. Anemia in hypothyroidism might result from bone marrow depression, decreased erythropoietin production, comorbid diseases, or concomitant iron, vitamin B12 or folate deficiency. Altered iron metabolism and oxidative stress may contribute to anemia in hyperthyroidism. The risk of anemia in autoimmune thyroid disease (AITD) may be posed by pernicious anemia and atrophic gastritis, celiac disease, autoimmune hemolytic syndrome, or rheumatic disorders. The simultaneous occurrence of anemia and thyroid disease, as well as their close relation, make the diseases an important clinical problem. The aim of the study is to provide a comprehensive review summarizing data on the prevalence, potential mechanisms, and therapy of anemia in the course of thyroid diseases from the clinical and pathogenetic perspective. Thyroid dysfunction and autoimmune thyroid disease should be considered in differential diagnosis of treatment-resistant or refractory anemia, as well as in case of increased red blood cell distribution width (RDW). Of note is that the presence of AITD itself, independently from thyroid hormonal status, might affect hemoglobin level.

  3. Anemia of Inflammation and Chronic Disease

    MedlinePlus

    Anemia of Inflammation and Chronic Disease National Hematologic Diseases Information Service What is anemia? Anemia is a condition in which a person has ... also cause low blood iron levels. People with anemia may feel tired because their blood does not ...

  4. Anemia

    MedlinePlus

    ... anemia, iron deficiency, iron deficiency anemia, iron supplementation, kidney disease, low blood iron, low iron, normocytic anemia, nutrition, pregnancy, Procrit, red blood cell deficiency, rheumatoid arthritis, thyroiditis ...

  5. Anemia in inflammatory bowel disease.

    PubMed

    Giannini, S; Martes, C

    2006-09-01

    Anemia is a frequent extraenteric complication of inflammatory bowel disease (IBD, Crohn's disease and ulcerative colitis). A systematic review of the literature shows that the overall prevalence of anemia ranges from 8.8% to 73.7% but differs whether in a setting of Crohn's disease or ulcerative colitis. A disabling complication of IBD, anemia worsens the patient's general condition and quality of life, and increases hospitalization rates. Different factors, including vitamin B12 and folic acid deficiency, bone marrow suppression secondary to drug therapy, autoimmune hemolytic anemia and the coexistence of myelodysplastic syndromes are involved in the pathogenesis of anemia in IBD. The main types of anemia in IBD are iron deficiency anemia and anemia accompanying chronic diseases. Correct diagnostic definition of anemia is a fundamental step in guiding the choice of therapeutic options, since the co-presence of different pathogenetic factors may sometimes require a more complex treatment plan. A review of anemia in IBD, its pathogenetic features, epidemiology, diagnosis and therapy based on evidence from recent studies is the focus of this article.

  6. The Lbw2 locus promotes autoimmune hemolytic anemia.

    PubMed

    Scatizzi, John C; Haraldsson, Maria K; Pollard, K Michael; Theofilopoulos, Argyrios N; Kono, Dwight H

    2012-04-01

    The lupus-prone New Zealand Black (NZB) strain uniquely develops a genetically imposed severe spontaneous autoimmune hemolytic anemia (AIHA) that is very similar to the corresponding human disease. Previous studies have mapped anti-erythrocyte Ab (AEA)-promoting NZB loci to several chromosomal locations, including chromosome 4; however, none of these have been analyzed with interval congenics. In this study, we used NZB.NZW-Lbw2 congenic (designated Lbw2 congenic) mice containing an introgressed fragment of New Zealand White (NZW) on chromosome 4 encompassing Lbw2, a locus previously linked to survival, glomerulonephritis, and splenomegaly, to investigate its role in AIHA. Lbw2 congenic mice exhibited marked reductions in AEAs and splenomegaly but not in anti-nuclear Abs. Furthermore, Lbw2 congenics had greater numbers of marginal zone B cells and reduced expansion of peritoneal cells, particularly the B-1a cell subset at early ages, but no reduction in B cell response to LPS. Analysis of a panel of subinterval congenic mice showed that the full effect of Lbw2 on AEA production was dependent on three subloci, with splenomegaly mapping to two of the subloci and expansions of peritoneal cell populations, including B-1a cells to one. These results directly demonstrated the presence of AEA-specific promoting genes on NZB chromosome 4, documented a marked influence of background genes on autoimmune phenotypes related to Lbw2, and further refined the locations of the underlying genetic variants. Delineation of the Lbw2 genes should yield new insights into both the pathogenesis of AIHA and the nature of epistatic interactions of lupus-modifying genetic variants.

  7. Anemia of chronic disease

    MedlinePlus

    ... disease Long-term infections, such as bacterial endocarditis, osteomyelitis (bone infection), HIV/AIDS , hepatitis B or hepatitis ... disease Crohn disease Erythropoietin test Juvenile idiopathic arthritis Osteomyelitis Rheumatic fever Ulcerative colitis Review Date 2/1/ ...

  8. [Anemia in chronic kidney disease].

    PubMed

    Amador-Medina, Lauro Fabián

    2014-01-01

    Anemia is almost unavoidable in the last stages of chronic kidney disease. It is defined as a condition where hemoglobin concentration is below 2 standard deviations from the mean hemoglobin level of the general population, corrected for age and sex (typically, hemoglobin < 13 g/dL in adults and 12 g/dL in women). Although the cause is multi-factorial, the most known is inadequate erythropoietin production. Anemia has been associated with poor prognosis in patients with several conditions such as cancer, chronic kidney disease and congestive heart failure. Treatment with erythropoiesis-stimulating agents, such as erythropoietin, is a logical strategy that has enabled clinical improvement and reduced transfusion requirements for the patients; however, total correction of anemia with erythropoiesis-stimulating agents has demonstrated an increase in the risk of mortality or cardiovascular complications associated with these agents. In randomized trials, the achievement of normal or nearly normal hemoglobin levels is not associated with improved survival and reduced cardiovascular risk; however the ideal hemoglobin level with the use of erythropoiesis-stimulating agents seems to be problematic. More information is needed in order to obtain definite conclusions; in the meantime, using the lowest possible dose of erythropoietin seems to be the most prudent approach.

  9. Anemia

    MedlinePlus

    ... problems) Long-term (chronic) diseases such as chronic kidney disease, cancer, ulcerative colitis, or rheumatoid arthritis Some forms of anemia, such as thalassemia or sickle cell anemia, which can be inherited Pregnancy Problems with bone marrow such as lymphoma, leukemia, ...

  10. Iron deficiency anemia in celiac disease.

    PubMed

    Freeman, Hugh James

    2015-08-21

    Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet.

  11. Iron deficiency anemia in celiac disease

    PubMed Central

    Freeman, Hugh James

    2015-01-01

    Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet. PMID:26309349

  12. Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

    PubMed

    Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

    2016-05-01

    Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.

  13. [Anemias in chronic obstructive pulmonary disease].

    PubMed

    Budnevsky, A V; Esaulenko, I E; Ovsyannikov, E S; Zhusina, Yu G

    2016-01-01

    According to different studies, anemia occurs in 8--33% of patients with chronic obstructive pulmonary disease (COPD). The paper describes the most important various causes of anemia in COPD, such as systemic inflammation and endocrine disorders, the use of some medications (theophylline, angiotensin-converting enzyme inhibitors), frequent COPD exacerbations, and long-term oxygen therapy. Lower hemoglobin levels in COPD patients are accompanied by increased shortness of breath, reduced exercise tolerance, and lower quality of life. Furthermore, some investigations have shown that anemia is an independent predictor of death in patients with COPD. In spite of the fact that anemia may be successfully in these patients, the evidence suggesting the importance of its impact on the prognosis of COPD is limited.

  14. [Biermer's disease and autoimmune hemolytic anemia].

    PubMed

    Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine

    2012-01-01

    Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old.

  15. Anemia Due to Excessive Bleeding

    MedlinePlus

    ... Anemia Due to Excessive Bleeding Iron Deficiency Anemia Vitamin Deficiency Anemia Anemia of Chronic Disease Aplastic Anemia Autoimmune ... Anemia Due to Excessive Bleeding Iron Deficiency Anemia Vitamin Deficiency Anemia Anemia of Chronic Disease Aplastic Anemia Autoimmune ...

  16. Iron deficiency anemia in inflammatory bowel disease

    PubMed Central

    Kaitha, Sindhu; Bashir, Muhammad; Ali, Tauseef

    2015-01-01

    Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia (IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used laboratory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and convenient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD. PMID:26301120

  17. Inter-ethnic polymorphism of the beta-globin gene locus control region (LCR) in sickle-cell anemia patients.

    PubMed

    Périchon, B; Ragusa, A; Lapouméroulie, C; Romand, A; Moi, P; Ikuta, T; Labie, D; Elion, J; Krishnamoorthy, R

    1993-06-01

    Sequence polymorphisms within the 5'HS2 segment of human locus control region is described among sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat are observed in strong linkage disequilibrium with each of the five major beta s haplotypes. Potential functional relevance of this polymorphic region in globin gene expression is discussed.

  18. [New insights on hepcidin in anemia of chronic disease].

    PubMed

    Wang, Feng-Dan; Zhou, Dao-Bin

    2009-12-01

    Anemia of chronic disease is normocytic and normochromic. One of the mechanisms is misbalance of iron metabolism. Hepcidin, a kind of protein secreted by liver is considered to be the hormone regulating iron metabolism. It binds to ferroportin and induces the latter one's internalization. Thus, iron transportation from iron storage cells to serum is reduced. Cytokines are elevated in chronic disease. They stimulate hepcidin expression in liver through JAK2/STAT3 pathway. As a result, iron absorption and reabsorption is blocked, which leads to the misbalance of iron metabolism in anemia of chronic disease. In this article, the hepcidin and its relation to iron metabolism and anemia in chronic disease are reviewed.

  19. Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus

    SciTech Connect

    Papadopoulo, D.; Guillouf, C.; Moustacchi, E. ); Mohrenweiser, H. )

    1990-11-01

    Fanconi anemia (FA) is an inherited human disorder associated with a predisposition to cancer and characterized by anomalies in the processing of DNA cross-links and certain monoadducts. The authors reported previously that the frequency of psoralen-photoinduced mutations at the HPRT locus is lower in FA cells than in normal cells. This hypomutability is shown here to be associated with an increased frequency of deletions in the HPRT gene when either a mixture of cross-links and monoadducts or monoadducts alone are induced. Molecular analysis of mutants in the HPRT gene was carried out. In normal cells the majority of spontaneous and induced mutants are point mutations whereas in FA deletion mutations predominate. In that case a majority of mutants were found to lack individual exons or small clusters of exons whereas in normal cells large (complete or major gene loss) and small deletions are almost equally represented. Thus they propose that the FA defect lies in a mutagenic pathway that, in normal cells, involves by passing lesions and subsequent gap filling by a recombinational process during replication.

  20. Anemias.

    PubMed

    Broadway-Duren, Jacqueline B; Klaassen, Hillary

    2013-12-01

    Anemias continue to present a challenge to the health care profession. Anemia is defined as a reduction in one or more of the RBC indices. Patients presenting with a mild form of anemia may be asymptomatic; however, in more serious cases the anemia can become life threatening. In many cases the clinical presentation also reflects the underlying cause. Anemia may be attributed to various causes, whereas autoimmune RBC destruction may be attributed to intrinsic and extrinsic factors. Laboratory tests are essential in facilitating early detection and differentiation of anemia.

  1. Diagnosing anemia in inflammatory bowel disease: beyond the established markers.

    PubMed

    Oustamanolakis, Pantelis; Koutroubakis, Ioannis E; Kouroumalis, Elias A

    2011-10-01

    The main types of anemia in inflammatory bowel disease (IBD) are iron deficiency anemia (IDA) and anemia of inflammatory etiology, or anemia of chronic disease (ACD). In the management of IBD patients with anemia it is essential for the physician to diagnose the type of anemia in order to decide in an evidence-based manner for the appropriate treatment. However, the assessment of iron status in IBD in many cases is rather difficult due to coexistent inflammation. For this assessment several indices and markers have been suggested. Ferritin, seems to play a central role in the definition and diagnosis of anemia in IBD and transferrin, transferrin saturation (Tsat), and soluble transferrin receptors are also valuable markers. All these biochemical markers have several limitations because they are not consistently reliable indices, since they are influenced by factors other than changes in iron balance. In this review, in addition to them, we discuss the newer alternative markers for iron status that may be useful when serum ferritin and Tsat are not sufficient. The iron metabolism regulators, hepcidin and prohepcidin, are still under investigation in IBD. Erythrocytes parameters like the red cell distribution width (RDW) and the percentage of hypochromic red cells as well as reticulocyte parameters such as hemoglobin concentration of reticulocytes, red blood cell size factor and reticulocyte distribution width could be useful markers for the evaluation of anemia in IBD.

  2. Anemia

    MedlinePlus

    ... also be iron deficient due to poor absorption. Vitamin-deficiency anemia may result from low levels of vitamin ... foods can help you avoid both iron-and vitamin-deficiency anemia. Foods to include in your diet include ...

  3. Anemia of Inflammation and Chronic Disease

    MedlinePlus

    ... AI/ACD may also be advised to take vitamin B12 and folic acid supplements. A person should talk ... and Nutrition People with anemia caused by iron, vitamin B12, or folic acid deficiencies are usually advised to ...

  4. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

    PubMed Central

    Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

    2015-01-01

    Abstract Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron. PMID:26061331

  5. Anemia

    MedlinePlus

    If you have anemia, your blood does not carry enough oxygen to the rest of your body. The most common cause of anemia is not having enough ... rich protein that gives the red color to blood. It carries oxygen from the lungs to the ...

  6. Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia.

    PubMed

    Cheng, Pan-pan; Jiao, Xiao-yang; Wang, Xue-hua; Lin, Jing-hua; Cai, Ying-mu

    2011-03-01

    Hepcidin is a key hormone governing mammalian iron homeostasis and may be directly or indirectly involved in the development of most iron deficiency/overload and inflammation-induced anemia. The objective of this study was to investigate the expression of hepcidin in anemia of chronic disease. To characterize serum hepcidin, iron and inflammatory indicators associated with anemia of chronic disease (ACD), we studied ACD, ACD concomitant iron-deficiency anemia (ACD/IDA), pure IDA and acute inflammation (AcI) patients and analyzed the associations between hepcidin levels and inflammation parameters in various types of anemia. Serum hepcidin levels in patient groups were statistically different, from high to low: ACD, AcI > ACD/IDA > the control > IDA. Serum ferritin levels were significantly increased in ACD and AcI patients but were decreased significantly in ACD/IDA and IDA. Elevated serum EPO concentrations were found in ACD, ACD/IDA and IDA patients but not in AcI patients and the controls. A positive correlation between hepcidin and IL-6 levels only existed in ACD/IDA, AcI and the control groups. A positive correlation between hepcidin and ferritin was marked in the control group, while a negative correlation between hepcidin and ferritin was noted in IDA. The significant negative correlation between hepcidin expression and reticulocyte count was marked in both ACD/IDA and IDA groups. All of these data demonstrated that hepcidin might play role in pathogenesis of ACD, ACD/IDA and IDA, and it could be a potential marker for detection and differentiation of these anemias.

  7. Anemia of chronic disease: illness or adaptive mechanism.

    PubMed

    Županić-Krmek; Sučić, Mirna; Bekić, Dinko

    2014-09-01

    The anemia of chronic disease (ACD) is the most prevalent anemia after iron deficiency anemia. It is associated with infectious, inflammatory and neoplastic disease. ACD is a medical condition caused by the release of cytokines which mediate inflammatory and immune response (tumor necrosis factor, interleukins 1 and 6, and interferon). Abnormal iron metabolism with iron trapping in reticuloendothelial cells is primarily the cause of this condition, making iron unavailable for erythropoiesis although iron tissue reserves are elevated. Disorder in erythropoietin secretion and shortening of red cell life span also play a role in the pathogenesis of ACD. The main therapy is treatment of the underlying disorder and red cell transfusions in severe anemia. In more severe (protracted) anemias that lead to impaired quality of life and have an impact on the mortality and survival rate, erythropoiesis stimulating agents are used. Recently, new possibilities are being evaluated in terms of therapy for ACD in defined conditions, such as chelating agents, as well as hepcidin antagonist and other erythropoiesis stimulating agents.

  8. Periodontal disease and anemias associated with Crohn's disease. A case report.

    PubMed

    Nagpal, Swati; Acharya, Anirudh B; Thakur, Srinath L

    2012-03-01

    Crohn's disease (CD) is an inflammatory bowel disease with oral findings, including periodontal manifestations. Anemias, such as iron deficiency and anemia of chronic disease (ACD), are the most common hematologic complications of CD. Periodontitis has systemic effects, and may tend toward anemia, which can be explained by depressed erythropoiesis. In the report presented here, the authors review a case of Crohn's disease diagnosed 10 years previous to the patient presenting with a changing anemic profile and periodontal disease. A discussion of patient and disease management is included.

  9. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  10. Inflammation associated anemia and ferritin as disease markers in SLE

    PubMed Central

    2012-01-01

    Introduction In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia. Methods A protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls. To confirm these results as well as the role of the iron transfer pathway in SLE, ELISAs were performed to measure ferritin and transferrin levels in inactive or active SLE patients and healthy controls. The relationship between ferritin/transferrin levels and inflammatory markers and anemia was next analyzed. Results Protein array results showed elevated ferritin levels in the serum and urine of lupus patients as compared to controls, which were further validated by ELISA. Increased ferritin levels correlated with measures of disease activity and anemia as well as inflammatory cytokine titers. Though active SLE patients had elevated urine transferrin, serum transferrin was reduced. Conclusion Urine ferritin and transferrin levels are elevated significantly in SLE patients and correlate with disease activity, bolstering previous reports. Most importantly, these changes correlated with the inflammatory state of the patients and anemia of chronic disease. Taken together, altered iron handling, inflammation and anemia of chronic disease constitute an ominous triad in SLE. PMID:22871034

  11. [Health locus of control of patients in disease management programmes].

    PubMed

    Schnee, M; Grikscheit, F

    2013-06-01

    Health locus of control beliefs plays a major role in improving self-management skills of the chronically ill - a main goal in disease management programmes (DMP). This study aims at characterising participants in disease management regarding their health locus of control. Data are based on 4 cross-sectional postal surveys between spring and autumn of 2006 and 2007 within the Health Care Monitor of the Bertelsmann Foundation. Among the 6 285 respondents, 1 266 are chronically ill and not enrolled in a DMP and 327 are participating in a DMP. A high internal locus of control (HLC) occurs significantly less often in DMP patients than in normal chronically ill patients (and healthy people) controlling for age, gender and social class. With increasing age, a high internal locus of control is also significantly less likely. When comparing healthy people, the chronically ill and the DMP participants a social gradient of a high internal locus of control belief can be observed. The weaker internal and higher doctor-related external locus of control of DMP participants should be carefully observed by the physician when trying to strengthen the patients' self-management skills. Evaluators of DMP should take into account the different baselines of DMP patients and relevant control groups and incorporate these differences into the evaluation.

  12. Anemia

    MedlinePlus

    ... Adults Making Your Wishes Known Home & Community Home › Aging & Health A to Z › Anemia Font size A A A Print Share Glossary Basic Facts & Information Causes & Symptoms Diagnosis & Tests Care & Treatment Lifestyle & Management Other Resources Caregiving How ...

  13. Sickle cell anemia with moyamoya disease: outcomes after EDAS procedure.

    PubMed

    Fryer, Robert H; Anderson, Richard C; Chiriboga, Claudia A; Feldstein, Neil A

    2003-08-01

    Moyamoya disease is a relatively uncommon neurovascular complication of sickle cell anemia. We report a case series of six patients with sickle cell anemia who developed moyamoya disease and underwent encephaloduroarteriosynangiosis procedures. These six patients presented with either cerebrovascular accidents, transient ischemic attacks, or seizures, and subsequent magnetic resonance imaging scans were suggestive of moyamoya-like changes in the cerebral vasculature. Conventional cerebral angiography was used to confirm the diagnosis in all six patients. Four of six patients manifested a cerebrovascular accident before surgery, and two of these patients were compliant on a transfusion protocol at the time of their cerebrovascular accident. Bilateral (n = 4) or unilateral (n = 2) encephaloduroarteriosynangiosis procedures were performed without any complications. The patient who was stroke-free preoperatively had a cerebrovascular accident 2 weeks after the procedure; otherwise, all patients have remained free of neurovascular complications with an average follow-up of 33 months. Collateral anastomoses between external and internal carotid arteries were established by magnetic resonance angiography in three patients. The encephaloduroarteriosynangiosis procedure is a safe and effective treatment option in patients with sickle cell anemia who develop moyamoya disease.

  14. Anemia in Inflammatory Bowel Disease Outpatients: Prevalence, Risk Factors, and Etiology

    PubMed Central

    Antunes, Carla Valéria de Alvarenga; Hallack Neto, Abrahão Elias; Nascimento, Cristiano Rodrigo de Alvarenga; Chebli, Liliana Andrade; Moutinho, Ivana Lúcia Damásio; Pinheiro, Bruno do Valle; Reboredo, Maycon Moura; Malaguti, Carla; Castro, Antonio Carlos Santana; Chebli, Júlio Maria Fonseca

    2015-01-01

    Anemia is common in inflammatory bowel disease (IBD). However, epidemiological studies of nonwestern IBD populations are limited and may be confounded by demographic, socioeconomic, and disease-related influences. This study evaluated the prevalence, risk factors, and etiology of anemia in Brazilian outpatients with IBD. Methods. In this cross-sectional study, 100 Crohn's disease (CD) patients and 100 ulcerative colitis (UC) subjects were assessed. Anemia workup included complete blood count, ferritin, transferrin saturation, serum levels of folic acid and vitamin B12, and C-reactive protein (CRP) concentration. Results. The overall prevalence of anemia in IBD was 21%. There was no significant difference in the prevalence of anemia between CD subjects (24%) and UC (18%). Moderate disease activity (OR: 3.48, 95% CI, 1.95–9.64, P = 0.002) and elevated CRP levels (OR: 1.8, 95% CI, 1.04–3.11, P = 0.02) were independently associated with anemia. The most common etiologies of anemia found in both groups were iron deficiency anemia (IDA; 10% on CD and 6% on UC) followed by the anemia of chronic disease (ACD; 6% for both groups). Conclusions. In Brazilian IBD outpatients, anemia is highly concurrent condition. Disease moderate activity as well as increased CRP was strongly associated with comorbid anemia. IDA and/or ACD were the most common etiologies. PMID:25705682

  15. Neocytolysis contributes to the anemia of renal disease

    NASA Technical Reports Server (NTRS)

    Rice, L.; Alfrey, C. P.; Driscoll, T.; Whitley, C. E.; Hachey, D. L.; Suki, W.

    1999-01-01

    Neocytolysis is a recently described physiological process affecting the selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin (EPO) depression appears to initiate the process, providing the rationale to investigate its contributions to the anemia of renal disease. When EPO therapy was withheld, four of five stable hemodialysis patients showed chromium 51 (51Cr)-red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these four patients received oral 13C-glycine and 15N-glycine, and there was a suggestion of pathological isotope enrichment of stool porphyrins when EPO therapy was held, again supporting selective hemolysis of newly released red cells that take up the isotope (one patient had chronic hemolysis indicated by isotope studies of blood and stool). Thus, neocytolysis can contribute to the anemia of renal disease and explain some unresolved issues about such anemia. One implication is the prediction that intravenous bolus EPO therapy is metabolically and economically inefficient compared with lower doses administered more frequently subcutaneously.

  16. Neocytolysis Contributes to the Anemia of Renal Disease

    NASA Technical Reports Server (NTRS)

    Rice, Lawrence; Alfrey, Clarence P.; Driscoll, Theda; Whitley, Carl E.; Hachey, David; Suki, Wadi

    1997-01-01

    Neocytolysis is a recently described physiologic process effecting selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin depression appears to initiate the process, providing rationale to investigate its contributions to the anemia of renal disease. When erythropoietin therapy was withheld, four of five stable hemodialysis patients demonstrated Cr-51 red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these patients received oral (13)C-glycine and (15)N-glycine and showed pathologic enrichment of stool porphyrins by the most recently ingested isotope when EPO therapy was held. This confirms selective hemolysis of newly-released red cells. (One patient had chronic hemolysis by isotope studies of blood and stool.) Thus, neocytolysis can contribute to the anemia of renal disease and explains some unresolved issues about such anemia. One implication is the prediction that intravenous bolus erythropoietin therapy is metabolically and economically inefficient compared to lower doses given more frequently subcutaneously.

  17. PREFERRED RETINAL LOCUS IN MACULAR DISEASE

    PubMed Central

    GREENSTEIN, VIVIENNE C.; SANTOS, RODRIGO A. V.; TSANG, STEPHEN H.; SMITH, R. THEODORE; BARILE, GAETANO R.; SEIPLE, WILLIAM

    2009-01-01

    Purpose To investigate the location and fixation stability of preferred retinal locations (PRLs) in patients with macular disease, and the relationship among areas of abnormal fundus autofluorescence, the PRL and visual sensitivity. Methods Fifteen patients (15 eyes) were studied. Seven had Stargardt disease, 1 bull’s eye maculopathy, 5 age-related macular degeneration, 1 Best disease, and 1 pattern dystrophy. All tested eyes had areas of abnormal fundus autofluorescence. The PRL was evaluated with fundus photography and the Nidek microperimeter. Visual field sensitivity was measured with the Nidek microperimeter. Results Of the 15 eyes, 4 had foveal and 11 had eccentric fixation. Eccentric PRLs were above the atrophic lesion and their stability did not depend on the degree of eccentricity from the fovea. Visual sensitivity was markedly decreased in locations corresponding to hypofluorescent areas. Sensitivity was not decreased in hyperfluorescent areas corresponding to flecks but was decreased if hyperfluorescence was in the form of dense annuli. Conclusion Eccentric PRLs were in the superior retina in regions of normal fundus autofluorescence. Fixation stability was not correlated with the degree of eccentricity from the fovea. To assess the outcomes of treatment trials it is important to use methods that relate retinal morphology to visual function. PMID:18628727

  18. Diagnosis and treatment of anemia in patients with inflammatory bowel disease

    PubMed Central

    Mücke, Victoria; Mücke, Marcus M.; Raine, Tim; Bettenworth, Dominik

    2017-01-01

    Anemia represents one of the most frequent complications in inflammatory bowel disease (IBD) and severely impairs the quality of life of affected patients. The etiology of anemia in IBD patients can be multifactorial, often involving a combination of iron deficiency (ID) and anemia of chronic disease (ACD). Although current guidelines recommend screening for and treatment of anemia in IBD patients, current observational data suggest that it still remains underdiagnosed and undertreated. Besides basic laboratory parameters (e.g. mean corpuscular volume, reticulocyte count, serum ferritin, transferrin saturation, etc.), the concentration of soluble transferrin receptor (sTfR) and novel parameters such as the sTfR/log ferritin index can guide the challenging task of differentiating between ID and ACD. Once identified, causes of anemia should be treated accordingly. This review summarizes our current understanding of anemia in IBD patients, including the underlying pathology, diagnostic approaches and appropriate anemia treatment regimens. PMID:28042234

  19. [Mecobalamin improved pernicious anemia in an elderly individual with Hashimoto's disease and diabetes mellitus].

    PubMed

    Izumi, Kenichi; Fujise, Takehiro; Inoue, Kanako; Mori, Hitoe; Yamazaki, Kouta; Hongou, Yui; Takagi, Satoko; Yamanouchi, Hiroko; Ashida, Kenji; Anzai, Keizo

    2013-01-01

    A 73-year-old Japanese man with Hashimoto's disease and diabetes mellitus received regular medical checkups for type 2 diabetes care. Blood tests indicated macrocytic anemia (red blood cell count, 279×104 /μL; hemoglobin, 12.2 g/dL; hematocrit, 34.0%; mean corpuscular volume, 121.9 fL). The laboratory data demonstrated a normal folic acid level with a low vitamin B12 level. An endoscopic examination indicated no signs of gastric or intestinal bleeding. Positive results for anti-intrinsic factor antibodies were strongly suggestive of pernicious anemia. The patient refused cobalamin injections to treat the anemia. However, the oral administration of mecobalamin for the treatment of diabetic neuropathy was simultaneously initiated. Subsequently, the anemia gradually improved. Oral mecobalamin was presumably effective for pernicious anemia management. Anemia is frequently observed in elderly patients, and the incidence of pernicious anemia increases with age. Anemia is conventionally treated with cobalamin injections. Currently, the oral administration of mecobalamin is not the typical treatment for anemia. However, as in our case, a few reports have documented positive results following oral mecobalamin treatment. Moreover, oral mecobalamin is a fairly recent, novel, noninvasive mode of treatment, making it ideal for elderly patients, who are generally frail. This case suggests the efficacy of mecobalamin for the treatment of pernicious anemia.

  20. [Sickle cell anemia causes varied symptoms and high morbidity. Serious prognosis in the most common genetic disease in the world].

    PubMed

    Kjellander, Christian; Sennström, Maria K B; Stiller, Viveka; Ågren, Anna

    2015-03-03

    Sickle cell anemia is a life-threatening disease, and the most common genetic disease in the world. The prevalence of sickle cell anemia in Sweden is unknown. Sickle cell anemia is an important disease, because of its variable complications, in many medical and surgical specialties. The overview highlights common medical problems encountered in sickle cell anemia presented through a case report of a pregnant woman.

  1. Anemia in inflammatory bowel disease: a neglected issue with relevant effects.

    PubMed

    Guagnozzi, Danila; Lucendo, Alfredo J

    2014-04-07

    Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients.

  2. Sideroblastic anemia as a preleukemic event in patients treated for Hodgkin's disease

    SciTech Connect

    Kitahara, M.; Cosgriff, T.M.; Eyre, H.J.

    1980-05-01

    Sideroblastic anemia after treatment for Hodgkin's disease was seen in two patients 3 years after completion of radiation therapy and chemotherapy. This was followed in both by the development of myelomonoblastic leukemia. No evidence of recurrent Hodgkin's disease was present in either patient. Our observation suggests that development of sideroblastic anemia in patients previously treated for Hodgkin's disease is probably secondary to the treatment and is a preleukemic event.

  3. Multipoint mapping of the central core disease locus

    SciTech Connect

    Schwemmle, S.; Wolff, K.; Grimm, T.; Mueller, C.R. ); Palmucci, L.M. ); Lehmann-Horn, F. ); Huebner, Ch. ); Hauser, E. ); Iles, D.E. ); MacLennan, D.H. )

    1993-07-01

    A linkage analysis with 12 DNA markers from proximal 19q was performed in eight families with central core disease (CCO). Two-point analysis gave a peak lod score of Z = 4.95 at [theta] = 0.00 for the anonymous marker D19S190 and of Z = 2.53 at [theta] = 0.00 for the ryanodine receptor (RYR1) candidate gene. Multipoint linkage data place the CCO locus at 19q13.1, flanked proximally by D19S191/D19S28 and distally by D19S47. This map location includes the RYR1 gene. The results of the linkage study present no evidence for genetic heterogeneity of CCO. 19 refs., 2 figs., 1 tab.

  4. Prevalence and Prognosis of Anemia in Dogs with Degenerative Mitral Valve Disease.

    PubMed

    Yu, Ivarosa Bing-Ye; Huang, Hui-Pi

    2016-01-01

    In humans, heart failure (HF) and renal insufficiency (RI) have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD) was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York Heart Association (NYHA) class IV HF (33.3%), followed by classes III (15.2%) and II (0%; p < 0.001). The presence of anemia was associated with HF severity and blood creatinine > 1.6 mg/dL (both p < 0.001). Anemic dogs had a shorter median survival [13 months; 95% confidence interval (CI): 0.7-19.1] than nonanemic dogs (28 months; 95% CI: 15.3-40.7; p < .001). NYHA class IV (hazard ratio (HR): 3.1, 95% CI: 2.2-4.3; p < 0.001), left atrium/aorta ratio > 1.7 (HR: 2.7, 95% CI: 1.7-4.2; p = 0.001), and presence of anemia (HR: 1.43, 95% CI: 1.1-1.9; p = 0.004) emerged as predictors of mortality. A cardiorenal-anemia syndrome-like triangle was observed and anemia was a prognostic factor for survival in dogs with DMVD.

  5. Prevalence and Prognosis of Anemia in Dogs with Degenerative Mitral Valve Disease

    PubMed Central

    Yu, Ivarosa Bing-Ye

    2016-01-01

    In humans, heart failure (HF) and renal insufficiency (RI) have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD) was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York Heart Association (NYHA) class IV HF (33.3%), followed by classes III (15.2%) and II (0%; p < 0.001). The presence of anemia was associated with HF severity and blood creatinine > 1.6 mg/dL (both p < 0.001). Anemic dogs had a shorter median survival [13 months; 95% confidence interval (CI): 0.7–19.1] than nonanemic dogs (28 months; 95% CI: 15.3–40.7; p < .001). NYHA class IV (hazard ratio (HR): 3.1, 95% CI: 2.2–4.3; p < 0.001), left atrium/aorta ratio > 1.7 (HR: 2.7, 95% CI: 1.7–4.2; p = 0.001), and presence of anemia (HR: 1.43, 95% CI: 1.1–1.9; p = 0.004) emerged as predictors of mortality. A cardiorenal-anemia syndrome-like triangle was observed and anemia was a prognostic factor for survival in dogs with DMVD. PMID:27840827

  6. Fanconi Anemia Research Fund

    MedlinePlus

    ... Support Publications Fundraising News What is the Fanconi Anemia Research Fund? Fanconi anemia is an inherited disease that can lead to ... population. Lynn and Dave Frohnmayer started the Fanconi Anemia Research Fund, in 1989 to find effective treatments ...

  7. Cooley's Anemia Foundation

    MedlinePlus

    ... role in their lives. Welcome to the Cooley's Anemia Foundation Website The Cooley's Anemia Foundation is dedicated to serving people afflicted with ... major form of this genetic blood disease, Cooley's anemia/thalassemia major. Our mission is advancing the treatment ...

  8. Living with Anemia

    MedlinePlus

    ... page from the NHLBI on Twitter. Living With Anemia Often, you can treat and control anemia. If ... by an inherited or chronic disease or trauma. Anemia and Children/Teens Infants and young children have ...

  9. Hematologic manifestations of systemic disease (including iron deficiency, anemia of inflammation and DIC).

    PubMed

    Witmer, Char M

    2013-12-01

    A complete blood cell count (CBC) is a frequent test sent to aid in the diagnostic evaluation of ill patients. Not uncommonly hematologic abnormalities may be the first sign of an underlying systemic disorder. The astute clinician needs to understand how systemic disease can affect the CBC to direct further diagnostic investigations. This article focuses on the 2 most common acquired anemias including iron deficiency and anemia of inflammation as well as disseminated intravascular coagulation.

  10. Prevalence of High Blood Pressure, Heart Disease, Thalassemia, Sickle-Cell Anemia, and Iron-Deficiency Anemia among the UAE Adolescent Population

    PubMed Central

    Barakat-Haddad, Caroline

    2013-01-01

    This study examined the prevalence of high blood pressure, heart disease, and medical diagnoses in relation to blood disorders, among 6,329 adolescent students (age 15 to 18 years) who reside in the United Arab Emirates (UAE). Findings indicated that the overall prevalence of high blood pressure and heart disease was 1.8% and 1.3%, respectively. Overall, the prevalence for thalassemia, sickle-cell anemia, and iron-deficiency anemia was 0.9%, 1.6%, and 5%, respectively. Bivariate analysis revealed statistically significant differences in the prevalence of high blood pressure among the local and expatriate adolescent population in the Emirate of Sharjah. Similarly, statistically significant differences in the prevalence of iron-deficiency anemia were observed among the local and expatriate population in Abu Dhabi city, the western region of Abu Dhabi, and Al-Ain. Multivariate analysis revealed the following significant predictors of high blood pressure: residing in proximity to industry, nonconventional substance abuse, and age when smoking or exposure to smoking began. Ethnicity was a significant predictor of heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia. In addition, predictors of thalassemia included gender (female) and participating in physical activity. Participants diagnosed with sickle-cell anemia and iron-deficiency anemia were more likely to experience different physical activities. PMID:23606864

  11. Prevalence of high blood pressure, heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia among the UAE adolescent population.

    PubMed

    Barakat-Haddad, Caroline

    2013-01-01

    This study examined the prevalence of high blood pressure, heart disease, and medical diagnoses in relation to blood disorders, among 6,329 adolescent students (age 15 to 18 years) who reside in the United Arab Emirates (UAE). Findings indicated that the overall prevalence of high blood pressure and heart disease was 1.8% and 1.3%, respectively. Overall, the prevalence for thalassemia, sickle-cell anemia, and iron-deficiency anemia was 0.9%, 1.6%, and 5%, respectively. Bivariate analysis revealed statistically significant differences in the prevalence of high blood pressure among the local and expatriate adolescent population in the Emirate of Sharjah. Similarly, statistically significant differences in the prevalence of iron-deficiency anemia were observed among the local and expatriate population in Abu Dhabi city, the western region of Abu Dhabi, and Al-Ain. Multivariate analysis revealed the following significant predictors of high blood pressure: residing in proximity to industry, nonconventional substance abuse, and age when smoking or exposure to smoking began. Ethnicity was a significant predictor of heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia. In addition, predictors of thalassemia included gender (female) and participating in physical activity. Participants diagnosed with sickle-cell anemia and iron-deficiency anemia were more likely to experience different physical activities.

  12. Evaluation of erythrocyte and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease

    PubMed Central

    Torino, Ana Beatriz Barbosa; Gilberti, Maria de Fátima Pererira; da Costa, Edvilson; de Lima, Gisélia Aparecida Freire; Grotto, Helena Zerlotti Wolf

    2015-01-01

    Objective The aim of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters to identify three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency. Methods Peripheral blood cells from 117 adult patients with anemia were classified according to iron status, inflammation, and hemoglobinopathies as: iron deficiency anemia (n = 42), anemia of chronic disease (n = 28), anemia of chronic disease associated with iron deficiency anemia (n = 22), and heterozygous β-thalassemia (n = 25). The percentage of microcytic erythrocytes, hypochromic erythrocytes, and the levels of hemoglobin in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating anemia. Results There was no difference between the groups of iron deficiency and anemia of chronic disease associated with absolute iron deficiency for any of the parameters. The percentage of hypochromic erythrocytes was the best parameter to identify absolute iron deficiency in patients with anemia of chronic disease (area under curve = 0.785; 95% confidence interval: 0.661–0.909 with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic erythrocyte count minus hypochromic erythrocyte count was very accurate to differentiate iron deficiency anemia from heterozygous β-thalassemia (area under curve = 0.977; 95% confidence interval: 0.950–1.005 with a sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8). Conclusion The erythrocyte and reticulocyte indices are moderately good to identify absolute iron deficiency in patients with anemia of chronic disease. PMID:25818816

  13. Evaluation of red cell and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease

    PubMed Central

    Torino, Ana Beatriz Barbosa; Gilberti, Maria de Fátima Pererira; da Costa, Edvilson; de Lima, Gisélia Aparecida Freire; Grotto, Helena Zerlotti Wolf

    2014-01-01

    Objective The purpose of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters under three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency. Methods Peripheral blood cells from 117 adult patients with anemia were classified according to iron status, and inflammatory activity, and the results of a hemoglobinopathy investigation as: iron deficiency anemia (n = 42), anemia of chronic disease (n = 28), anemia of chronic disease associated with iron deficiency anemia (n = 22), and heterozygous β thalassemia (n = 25). The percentage of microcytic red cells, hypochromic red cells, and levels of hemoglobin content in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating between the different types of anemia. Results There was no significant difference between the iron deficient group and anemia of chronic disease associated with absolute iron deficiency in respect to any parameter. The percentage of hypochromic red cells was the best parameter to discriminate anemia of chronic disease with and without absolute iron deficiency (area under curve = 0.785; 95% confidence interval: 0.661–0.909, with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic red cells minus hypochromic red cells was very accurate in differentiating iron deficiency anemia and heterozygous β thalassemia (area under curve = 0.977; 95% confidence interval: 0.950–1.005; with sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8). Conclusion The indices related to red cells and reticulocytes have a moderate performance in identifying absolute iron deficiency in patients with anemia of chronic disease. PMID:25453653

  14. Hemoglobin C, S-C, and E Diseases

    MedlinePlus

    ... Anemia Due to Excessive Bleeding Iron Deficiency Anemia Vitamin Deficiency Anemia Anemia of Chronic Disease Aplastic Anemia Autoimmune ... Anemia Due to Excessive Bleeding Iron Deficiency Anemia Vitamin Deficiency Anemia Anemia of Chronic Disease Aplastic Anemia Autoimmune ...

  15. Anemia and end-stage renal disease in the developing world.

    PubMed

    Maïz, Hédi Ben; Abderrahim, Ezzeddine; Zouaghi, Karim

    2002-09-01

    In developing countries, multiple comorbidities such as malnutrition, parasitoses, and hemoglobinopathies contribute to the aggravation of anemia observed in patients with end-stage renal diseases. We analyze here the results of a retrospective evaluation of red-cells indices and iron parameters conducted at the end of December 2000 in 304 prevalent Tunisian patients (sex ratio, 1.05; mean age, 53.7 years) receiving chronic hemodialysis for a median duration of 49.6 months (range, 1.6 to 278). Anemia, observed in 87.8% of patients, was normochromic and normocytic in 73% of cases. Only 2% of patients had microcytic and hypochromic anemia. Iron deficiency was observed in 21.6% of anemic patients. The mean rate of hemoglobin was significantly higher in men and in patients with polycystic kidney disease as the cause of renal failure. There was a positive correlation between hemoglobin values and the quality of dialysis. Only 10.8% of patients were on recombinant human erythropoietin (rHuEPO) and 38% required regular transfusions. We conclude that anemia observed in our patients had, in most cases, the characteristics of renal anemia and could be attributed to a deficit of renal production of erythropoietin. However, for financial reasons, prescription of rHuEPO is rather restrictive and blood transfusion remains largely used. The nephrology community and dialysis providers should increase their efforts to improve the anemia care of dialyzed patients in developing countries.

  16. Management of iron deficiency anemia in inflammatory bowel disease - a practical approach.

    PubMed

    Stein, Jürgen; Dignass, Axel U

    2013-01-01

    Although anemia is the most common systemic manifestation of inflammatory bowel disease (IBD), among the broad spectrum of extraintestinal disease complications encountered in IBD, including arthritis and osteopathy, it has generally received little consideration. However, not only in terms of frequency, but also with regard to its potential effect on hospitalization rates and on the quality of life and work, anemia is indeed a significant and costly complication of IBD. Anemia is multifactorial in nature, the most prevalent etiological forms being iron deficiency anemia (IDA) and anemia of chronic disease. In a condition associated with inflammation, such as IBD, the determination of iron status using common biochemical parameters alone is inadequate. A more accurate assessment may be attained using new iron indices including reticulocyte hemoglobin content, percentage of hypochromic red cells or zinc protoporphyrin. While oral iron supplementation has traditionally been a mainstay of IDA treatment, it has also been linked to extensive gastrointestinal side effects and possible disease exacerbation. However, many physicians are still reluctant to administer iron intravenously, despite the wide availability of a variety of new IV preparations with improved safety profiles, and despite the recommendations of international expert guidelines. This article discusses improved diagnostic and therapeutic strategies based on new clinical insights into the regulation of iron homeostasis.

  17. An investigation of the role of immunologic factors in anemia associated with canine heartworm disease.

    PubMed

    Werner, L L; Halliwell, R E; Jackson, R F; Needham, T C; Limpach, M

    1984-10-01

    Direct Coombs' antiglobulin tests were performed on 80 dogs with patent Dirofilaria immitis infection and 170 dogs negative for microfilaria of D. immitis. Presence or absence of anemia was determined by hematocrit in 55 of the heartworm negative dogs and 68 of the dogs with heartworm disease. Heartworm infected dogs showed a higher incidence (37%) of anemia than noninfected dogs (14.5%). Anemia was most prevalent in two groups of dogs with heartworm infection, one group showing vena caval syndrome (91%) and the other occult dirofilariasis (62.5%). These latter two groups of dogs also showed a significantly higher number of positive Coombs' reactions at 37 degrees C than other dogs with heartworm disease and the noninfected dogs. The number of positive Coombs' reactions at 4 degrees C among the total of 80 dogs with heartworm infection was significantly higher than that for dogs without heartworm disease. However, there was no positive correlation between anemia and the outcome of the Coombs' test at either temperature. These findings do not suggest that immunologic factors play a major role in the pathogenesis of anemia in dogs with heartworm disease.

  18. [Hemolytic anemia as the first clinical presentation of Wilson disease: a pediatric case].

    PubMed

    Henao C, José A; Valverde Muñoz, Kathia; Ávila A, María L

    2016-12-01

    Wilson disease is an autosomal recessive disorder of the copper's hepatic metabolism; it results in toxicity due to accumulation of the mineral. The hemolytic anemia is present in 17% at some point of the disease, although it is a rare initial clinical presentation.

  19. Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease

    PubMed Central

    Li, Ya; Shi, Hao; Wang, Wei-Ming; Peng, Ai; Jiang, Geng-Ru; Zhang, Jin-Yuan; Ni, Zhao-Hui; He, Li-Qun; Niu, Jian-Ying; Wang, Nian-Song; Mei, Chang-Lin; Xu, Xu-Dong; Guo, Zhi-Yong; Yuan, Wei-Jie; Yan, Hai-Dong; Deng, Yue-Yi; Yu, Chen; Cen, Jun; Zhang, Yun; Chen, Nan

    2016-01-01

    Abstract This was the first multicenter, cross-sectional survey to assess the prevalence of anemia, patient awareness, and treatment status in China. Data of patients with chronic kidney disease (CKD; age, 18–75 years; both out- and inpatients) from 25 hospitals in Shanghai, seeking medical treatment at the nephrology department, were collected between July 1, 2012 and August 31, 2012. The prevalence, awareness, and treatment of anemia in patients with nondialysis CKD (ND-CKD) were assessed. Anemia was defined as serum hemoglobin (Hb) levels ≤12 g/dL in women and ≤13 g/dL in men. A total of 2420 patients with ND-CKD were included. Anemia was established in 1246 (51.5%) patients: 639 (51.3%) men and 607 (48.7%) women. The prevalence of anemia increased with advancing CKD stage (χ2trend = 675.14, P < 0.001). Anemia was more prevalent in patients with diabetic nephropathy (68.0%) than in patients with hypertensive renal damage (56.6%) or chronic glomerulonephritis (46.1%, both P < 0.001). Only 39.8% of the anemic patients received treatment with erythropoietin and 27.1% patients received iron products; furthermore, 22.7% of the patients started receiving treatment when their Hb level reached 7 g/dL. The target-achieving rate (Hb at 11–12 g/dL) was only 8.2%. Of the 1246 anemia patients, only 7.5% received more effective and recommended intravenous supplementation. Anemia is highly prevalent in patients with ND-CKD in China, with a low target-achieving rate and poor treatment patterns. The study highlights the need to improve multiple aspects of CKD management to delay the progression of renal failure. PMID:27310973

  20. Phagocytosis, oxidative burst, and produced reactive species are affected by iron deficiency anemia and anemia of chronic diseases in elderly.

    PubMed

    Paino, I M M; Miranda, J C; Marzocchi-Machado, C M; Cesarino, E J; de Castro, F A; de Souza, A M

    2009-01-01

    Iron and oxidative stress have a regulatory interplay. During the oxidative burst, phagocytic cells produce free radicals such as hypochlorous acid (HOCl). Nevertheless, scarce studies evaluated the effect of either iron deficiency anemia (IDA) or anemia of chronic disease (ACD) on phagocyte function in the elderly. The aim of the present study was to determine the oxidative burst, phagocytosis, and nitric oxide (*NO) and HOCl, reactive species produced by monocytes and neutrophils in elderly with ACD or IDA. Soluble transferrin receptor, serum ferritin, and soluble transferrin receptor/log ferritin (TfR-F) index determined the iron status. The study was constituted of 39 patients aged over 60 (28 women and 11 men) recruited from the Brazilian Public Health System. Oxidative burst fluorescence intensity per neutrophil in IDA group and HOCl generation in both ACD and IDA groups were found to be lower (p < 0.05). The percentages of neutrophils and monocytes expressing phagocytosis in ACD group were found to be higher (p < 0.05). There was an overproduction of *NO from monocytes, whereas the fundamental generation of HOCl appeared to be lower. Phagocytosis, oxidative burst, and *NO and HOCl production are involved in iron metabolism regulation in elderly patients with ACD and IDA.

  1. Approach to Anemia in Hospitalized Patients with Infectious Diseases; Is it Appropriate?

    PubMed

    Entezari-Maleki, Taher; Khalili, Hossein; Karimzadeh, Iman; Jafari, Sirous

    2015-01-01

    Anemia of chronic diseases (ACD) is a common problem in patients with infectious diseases and can influence the quality of life and patients' survival. Despite the clinical importance of ACD, data are still lacking regarding this problem in the infectious diseases. This study aimed to evaluate the prevalence, related factors, outcome and approaches to anemia in the infectious diseases ward. This retrospective study was performed to review the medical records of patients admitted to the infectious diseases department of Imam Khomeini hospital during a two-year period between 2009 and 2011. A standard protocol was developed to evaluate anemia. Patients' demographic data approaches to manage anemia and routine laboratory tests were recorded and compared with the protocol. Totally, 1,120 medical records were reviewed. ACD was recognized in 705 patients (63%). Only 5.1% of diagnostic and 8.7% of treatment approaches was based on the protocol. The majority of patients (89.4%) were received inappropriate treatment regarding. Mortality rate of patients with ACD was 3.4%. Moreover, a significant correlation between anemia and mortality was detected (r = 0.131; p = 0.026). A statistically significant correlation was also identified between patients' Hgb and ESR, CRP, reasons of admission, number of medications, and underlying diseases. In conclusion, results of this study suggested that ACD is a common problem in infectious diseases patients and significantly associated with patients' mortality. Moreover, the majority of studied patients were not received an appropriate diagnostic and treatment approach which arises more concerns regarding the management of ACD in infectious diseases setting.

  2. [Anemia and iron deficiency in children with chronic respiratory diseases].

    PubMed

    Barja, Salesa; Capo, Eduardo; Briceño, Lilian; Jakubson, Leticia; Méndez, Mireya; Becker, Ana

    2013-01-01

    Introducción: Los niños con enfermedades respiratorias crónicas (ERC) tienen mayor riesgo de desarrollar anemia ferropriva, sin embargo, la ferropenia está infradiagnosticada. Objetivos: Describir el status de hierro (Fe) en niños con ERC y evaluar la respuesta a su suplementación profiláctica. Método: Estudio prospectivo de niños con ERC y adecuada ingesta de Fe en la dieta: se realizó hemograma, velocidad de eritro-sedimentación, proteína Creactiva y perfil de Fe. Posteriormente, aquellos con hemoglobina plasmática (Hb) normal no se suplementaron con Fe (Grupo A) y los que presentaban anemia ferropriva o factores de riesgo sí lo fueron (grupo B). Se evaluaron al 3º mes, después se suplementaron todos y se re-evaluaron al 4ºmes. Resultados: De 40 pacientes, con mediana de edad 30 meses (0,5 a 178), 60% eran hombres, 80% eutróficos. Requerían ventilación prolongada u oxigenoterapia 45%. Diagnósticos: 50% Bronquiolitis Obliterante post-infecciosa, 17,5% enfermedades de la vía aérea, 10% Displasia Broncopulmonar, 7,5% Fibrosis Quística y 15% otros. Basalmente 12,5% tuvo bajos depósitos de Fe y 20% anemia (la mayoría ferropriva). Completaron el estudio 25 niños: el grupo A disminuyó la ferritina sérica al 3ºmes (- 22,9 ± 30) y aumentó al 4ºmes (+12,8 ± 26) μg/L, (p = 0,013), sin cambio en la Hb. El grupo B tuvo ascenso de la Hb (91 ± 12 a 102 ± 12% del promedio para la edad, p = 0,04). Conclusión: La anemia ferropriva y la ferropenia son frecuentes en niños con ERC, quienes deterioran reversiblemente sus depósitos si no son suplementados. Sugerimos monitorizar con perfil de Fe y tratar precozmente, o suplementarlos en forma profiláctica.

  3. Role of Hepcidin-25 in Chronic Kidney Disease: Anemia and Beyond.

    PubMed

    Ueda, Norishi; Takasawa, Kazuya

    2017-03-16

    Iron is an essential element for all living organisms, but produces toxic oxidants. Thus, iron homeostasis is tightly regulated in mammals. Hepcidin-25 (hepcidin) has emerged as a molecule that regulates iron metabolism. Binding of hepcidin to its receptor, ferroportin, inhibits intestinal iron absorption and iron efflux from hepatocytes and macrophages. Decreased hepcidin enhances iron absorption and efflux. Hepcidin could be predictive of iron status and the response to iron supplementation or erythropoietin-stimulating agents. Monitoring hepcidin is helpful for the management of anemia. Thus, it is urgent to obtain normal reference values in a large population of healthy subjects and to standardize various hepcidin assays, which enables to compare the data measured by different methods. Anemia is an important and common problem associated with chronic kidney disease (CKD), which is caused by erythropoietin deficiency, iron-restricted erythropoiesis, inflammation, hypoxia, vitamin D deficiency, hyperparathyroidism, and obesity. Anemia causes poor quality of life, progression of CKD, increased risk of cardiovascular events, and mortality. Besides its role for anemia, recent evidence suggests that hepcidin-25 plays a role in the pathogenesis and progression of kidney injury via modulation of iron-mediated oxidant injury. Despite accumulating experimental data, information about clinical significance of hepcidin-25 for anemia and kidney injury in CKD patients is scarce, especially in children. This review summarizes the current knowledge of a role of hepcidin-25 in the regulation of anemia and kidney injury in children and adults with CKD. Strategy for modulating hepcidin-25 to prevent anemia and kidney injury associated with CKD is also discussed.

  4. Postoperative Recurrence of Invasive Thymoma with Cold Agglutinin Disease and Autoimmune Hemolytic Anemia.

    PubMed

    Yoneda, Taro; Koba, Hayato; Tanimura, Kota; Ogawa, Naohiko; Watanabe, Satoshi; Hara, Johsuke; Abo, Miki; Sone, Takashi; Kimura, Hideharu; Kasahara, Kazuo

    A 50-year-old man presented to our hospital in 1995. Invasive thymoma was diagnosed and extended thymectomy and left upper lobe partial resection were performed. In 2013, he complained of dyspnea. Chest computed tomography showed postoperative recurrence of invasive thymoma. Several chemotherapies were administered. Severe anemia and an increase in the total bilirubin level were observed with chemotherapies. In additional, an examination showed that the direct Coombs test was positive. Cold agglutinin was also high. We herein experienced a rare case of postoperative recurrence of invasive thymoma with cold agglutinin disease and autoimmune hemolytic anemia.

  5. Bacillus cereus bacteremia and hemolytic anemia in a patient with hemoglobin SC disease.

    PubMed

    Rodgers, G M; Barrera, E; Martin, R R

    1980-08-01

    A patient with hemoglobin SC disease and cholelithiasis was found to have Bacillus cereus bacteremia. Hemolytic anemia developed, for which common causes of hemolysis were excluded, suggesting a relationship with the bacteremia. Following in vitro incubation, type O erythrocytes were hemolyzed by the culture, but not by a bacteria-free filtrate. This case confirms the association between sickle cell disorders and cholelithiasis with B cereus infections. In addition, it provides evidence for in vivo hemolysis with B cereus bacteremia, an organism not previously associated with hemolytic anemia.

  6. [Differential diagnosis of anemias].

    PubMed

    Szerafin, László; Jakó, János

    2005-02-13

    The authors describe the factors influencing of normal hemoglobin level, pathogenetic and morphological classification of anemias and the possibilities to distinguish their different types. They highlight features of iron deficiency anemia and anemia of chronic diseases. They summarise in tables the basis of laboratory diagnosis and possibility of identification of different types of anemias.

  7. Red blood cell abnormalities and the pathogenesis of anemia in end-stage renal disease.

    PubMed

    Georgatzakou, Hara T; Antonelou, Marianna H; Papassideri, Issidora S; Kriebardis, Anastasios G

    2016-08-01

    Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation. Uremic toxins severely affect RBC lifespan; however, the implicated molecular pathways are poorly understood. Moreover, current management of anemia in ESRD is controversial due to the "anemia paradox" phenomenon, which underlines the need for a more individualized approach to therapy. RBCs imprint the adverse effects of uremic, inflammatory, and oxidative stresses in a context of structural and functional deterioration that is associated with RBC removal signaling and morbidity risk. RBCs circulate in hostile plasma by raising elegant homeostatic defenses. Variability in primary defect, co-morbidity, and therapeutic approaches add complexity to the pathophysiological background of the anemic ESRD patient. Several blood components have been suggested as biomarkers of anemia-related morbidity and mortality risk in ESRD. However, a holistic view of blood cell and plasma modifications through integrated omics approaches and high-throughput studies might assist the development of new diagnostic tests and therapies that will target the underlying pathophysiologic processes of ESRD anemia.

  8. Sickle cell anemia

    MedlinePlus

    Anemia - sickle cell; Hemoglobin SS disease (Hb SS); Sickle cell disease ... Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S. Hemoglobin is a protein inside red blood cells ...

  9. Rheumatoid anemia.

    PubMed

    Masson, Charles

    2011-03-01

    Rheumatoid anemia is a typical example of anemia of chronic disease. It differs from other forms of anemia, such as iron deficiency anemia or iatrogenic anemia. Rheumatoid anemia is normochromic, normocytic or, less often, microcytic, aregenerative, and accompanied with thrombocytosis. Serum transferrin levels are normal or low, transferrin saturation is decreased, serum ferritin levels are normal or high, the soluble transferrin receptor (sTfR) is not increased (a distinguishing feature with iron deficiency anemia), and the sTfR/log ferritin ratio is lower than 1. This review discusses the prevalence and impact of rheumatoid anemia based on a review of the literature. Iron metabolism, absorption, diffusion, storage, and use by the bone marrow are described using published data on transferrin, ferritin, and hepcidin. Hepcidin is now recognized as a key factor in rheumatoid anemia, in conjunction with the cytokine interleukin-6 (IL-6). Hepcidin is a hormone that lowers serum iron levels and regulates iron transport across membranes, preventing iron from exiting the enterocytes, macrophages, and hepatocytes. In addition, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. The action of hepcidin is mediated by binding to the iron exporter ferroportin. Hepcidin expression in the liver is dependent on the protein hemojuvelin. Inflammation leads to increased hepcidin production via IL-6, whereas iron deficiency and factors associated with increased erythropoiesis (hypoxia, bleeding, hemolysis, dyserythropoiesis) suppress the production of hepcidin. Data from oncology studies and the effects of recombinant human IL-6 support a causal link between IL-6 production and the development of anemia in patients with chronic disease. IL-6 diminishes the proportion of nucleated erythroid cells in the bone marrow and lowers the serum iron level, and these abnormalities can be corrected by administering an IL-6 antagonist. IL-6 stimulates

  10. Serum phosphorus and association with anemia among a large diverse population with and without chronic kidney disease

    PubMed Central

    Tran, Lac; Batech, Michael; Rhee, Connie M.; Streja, Elani; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J.; Sim, John J.

    2016-01-01

    Background We hypothesized that phosphorus has an effect on anemia in both normal kidney function and early chronic kidney disease (CKD). We sought to determine whether higher phosphorus levels are associated with anemia in a large diverse population without CKD and early CKD. Methods This study is a historical population-based study within the Kaiser Permanente Southern California health system (1 January 1998 to 31 December 2013) among individuals aged 18 years and older with estimated glomerular filtration rate >30 mL/min/1.73 m2 and measurements of serum phosphorus, creatinine and hemoglobin. Individuals were excluded if they had secondary causes of anemia. Odds ratio (OR) estimated for moderate anemia defined as hemoglobin <11 g/dL for both sexes. Mild anemia was defined as <12 g/dL (females) and <13 g/dL (males). Results Among 155 974 individuals, 4.1% had moderate anemia and 12.9% had mild anemia. Serum phosphorus levels ≥3.5 mg/dL were associated with both mild and moderate anemia. Moderate anemia OR (95% confidence interval) was 1.16 (1.04–1.29) for every 0.5 mg/dL phosphorus increase and 1.26 (1.07–1.48) in the highest versus middle phosphorus tertile. Additional independent anemia risk factors, including female sex, Asian race, diabetes, low albumin and low iron saturation, were observed, but did not alter the anemia–phosphorus association. Conclusions Higher phosphorus levels were associated with a greater likelihood for anemia in a population with early CKD and normal kidney function. Phosphorus may be a biomarker for anemia and may affect aspects of hematopoiesis. PMID:26254460

  11. Who Is at Risk for Anemia?

    MedlinePlus

    ... Trials Links Related Topics Aplastic Anemia Hemolytic Anemia Iron-Deficiency Anemia Pernicious Anemia Sickle Cell Disease Send ... develop during pregnancy due to low levels of iron and folic acid (folate) and changes in the ...

  12. Sickle Cell Anemia (For Teens)

    MedlinePlus

    ... Can You Do to Stay Well? en español Anemia falciforme What Is Sickle Cell Disease? Sickle cell ... about 10 to 20 days. This usually causes anemia . Anemia is what happens when the body's number ...

  13. The APOE locus advances disease progression in late onset familial Alzheimer`s disease but is not causative

    SciTech Connect

    Crawford, F.; Bennett, C.; Osborne, A.

    1994-09-01

    An association has been observed in several independent data sets between late onset Alzheimer`s disease (AD) and the APOE locus on chromosomes 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the {epsilon}4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and nonstringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease-free survival suggested that APOE genotype contributes a small fraction of the total variance, indicating that the APOE locus is a poor predictor of disease-free survival time within late onset families. We suggest that the APOE locus enhances the rate of progression of the disease in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause this disease.

  14. A rare association of celiac disease and aplastic anemia: case report of a child and review of literature.

    PubMed

    Badyal, Rama Kumari; Sachdeva, Man Updesh Singh; Varma, Neelam; Thapa, Babu Ram

    2014-01-01

    An association between severe aplastic anemia and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus, and thyroid disorders. Herein we report a patient with celiac disease who was not strictly following a gluten-free diet and presented with progressive pallor, fever, and weakness of 1 month's duration. On investigation, he had pancytopenia, which on subsequent evaluation revealed aplastic anemia. An association between aplastic anemia and celiac disease has rarely been reported. To the best of author's knowledge, only 1 pediatric case of celiac disease associated with aplastic anemia has been published. This is the second report to suggest such an association in children.

  15. Dental Perspective of Rare Disease of Fanconi Anemia: Case Report with Review

    PubMed Central

    Goswami, Mridula; Bhushan, Urvashi; Goswami, Manoj

    2016-01-01

    Fanconi anemia is an extremely rare genetic disease characterized by chromosomal instability that induces congenital alterations in individuals. It causes defective hemopoiesis ultimately leading to bone marrow failure. Patients are susceptible to recurrent infections and increased risk of hemorrhage, as well as delayed and poor wound healing. Herein, we report a case of Fanconi anemia in which various classical signs of the disease were present. The patient has been on regular follow-up since three and a half years for management of dental problems. The different aspects of this rare disorder are discussed with emphasis on oral manifestations and their influence on the general health of affected patients. Due to an increased susceptibility to developing cancers in this specific population, it is imperative for pediatric dentists to know about the common oral manifestations and potentially cancerous lesions, in order to make an early diagnosis and provide comprehensive care and maintenance of oral health in affected individuals. PMID:27013901

  16. Lafora disease is not linked to the Unverricht-Lundborg locus.

    PubMed

    Labauge, P; Beck, C; Bellet, H; Coquillat, G; Vespignani, H; Dulac, O; Gilgenkrantz, S; Dravet, C; Genton, P; Pellissier, J F

    1995-02-27

    Lafora disease and Unverricht-Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht-Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North-African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht-Lundborg disease may be facilitated by molecular genetic analysis.

  17. Anti-M Antibody Induced Prolonged Anemia Following Hemolytic Disease of the Newborn Due to Erythropoietic Suppression in 2 Siblings.

    PubMed

    Ishida, Atsushi; Ohto, Hitoshi; Yasuda, Hiroyasu; Negishi, Yutaka; Tsuiki, Hideki; Arakawa, Takeshi; Yagi, Yoshihito; Uchimura, Daisuke; Miyazaki, Toru; Ohashi, Wataru; Takamoto, Shigeru

    2015-08-01

    Hemolytic disease of the newborn (HDN) arising from MNSs incompatibility is rare, with few reports of prolonged anemia and reticulocytopenia following HDN. We report the younger of 2 male siblings, both of whom had anti-M-induced HDN and anemia persisting for over a month. Peripheral reticulocytes remained inappropriately low for the degree of anemia, and they needed multiple red cell transfusions. Viral infections were ruled out. Corticosteroids were given for suspected pure red cell aplasia. Anemia and reticulocytopenia subsequently improved. Colony-forming unit erythroid assay revealed erythropoietic suppression of M antigen-positive erythroid precursor cells cultured with maternal or infant sera containing anti-M. In conclusion, maternal anti-M caused HDN and prolonged anemia by erythropoietic suppression in 2 siblings.

  18. Newly Diagnosed Anemia Increases Risk of Parkinson's disease: A Population-Based Cohort Study.

    PubMed

    Hong, Chien Tai; Huang, Yao Hsien; Liu, Hung Yi; Chiou, Hung-Yi; Chan, Lung; Chien, Li-Nien

    2016-07-14

    Anemia and low hemoglobin have been identified to increase Parkinson's disease (PD) risk. This population-based cohort study investigated PD risk in newly diagnosed anemic patients by using data from the Taiwan National Health Insurance Research Database. All newly diagnosed anemic patients (n = 86,334) without a history of stroke, neurodegenerative diseases, traumatic brain injury, major operations, or blood loss diseases were enrolled. A cohort of nonanemic controls, 1:1 matched with anemic patients on the basis of the demographics and pre-existing medical conditions, was also included. Competing risk analysis was used to evaluate PD risk in anemic patients compared with that in their matched controls. The adjusted hazard ratio (aHR) of PD risk in the anemic patients was 1.36 (95% confidence interval [CI]: 1.22-1.52, p < 0.001). Iron deficiency anemia (IDA) patients tended to exhibit a higher PD risk (aHR: 1.49; 95% CI: 1.24-1.79, p < 0.001). Furthermore, Iron supplement did not significantly affect the PD risk: the aHRs for PD risk were 1.32 (95% CI: 1.07-1.63, p < 0.01) and 1.86 (95% CI: 1.46-2.35, p < 0.001) in IDA patients with and without iron supplementation, respectively. The population-based cohort study indicated newly diagnosed anemia increases PD risk.

  19. The Cost-Effectiveness of Anemia Treatment for Persons with Chronic Kidney Disease

    PubMed Central

    Yarnoff, Benjamin O.; Hoerger, Thomas J.; Simpson, Siobhan A.; Pavkov, Meda E.; Burrows, Nilka R.; Shrestha, Sundar S.; Williams, Desmond E.; Zhuo, Xiaohui

    2016-01-01

    Background Although major guidelines uniformly recommend iron supplementation and erythropoietin stimulating agents (ESAs) for managing chronic anemia in persons with chronic kidney disease (CKD), there are differences in the recommended hemoglobin (Hb) treatment target and no guidelines consider the costs or cost-effectiveness of treatment. In this study, we explored the most cost-effective Hb target for anemia treatment in persons with CKD stages 3–4. Methods and Findings The CKD Health Policy Model was populated with a synthetic cohort of persons over age 30 with prevalent CKD stages 3–4 (i.e., not on dialysis) and anemia created from the 1999–2010 National Health and Nutrition Examination Survey. Incremental cost-effectiveness ratios (ICERs), computed as incremental cost divided by incremental quality adjusted life years (QALYs), were assessed for Hb targets of 10 g/dl to 13 g/dl at 0.5 g/dl increments. Targeting a Hb of 10 g/dl resulted in an ICER of $32,111 compared with no treatment and targeting a Hb of 10.5 g/dl resulted in an ICER of $32,475 compared with a Hb target of 10 g/dl. QALYs increased to 4.63 for a Hb target of 10 g/dl and to 4.75 for a target of 10.5 g/dl or 11 g/dl. Any treatment target above 11 g/dl increased medical costs and decreased QALYs. Conclusions In persons over age 30 with CKD stages 3–4, anemia treatment is most cost-effective when targeting a Hb level of 10.5 g/dl. This study provides important information for framing guidelines related to treatment of anemia in persons with CKD. PMID:27404556

  20. Circulating thrombopoietin levels in normal healthy blood donors and in aplastic anemia patients in relation to disease severity

    PubMed Central

    Singh, Abhay; Verma, Anupam; Nityanand, Soniya; Chaudhary, Rajendra; Elhence, Priti

    2015-01-01

    Background: Thrombopoietin (TPO) is the key hematopoietic growth factor regulating the production of platelets from bone marrow megakaryocytes and maintaining platelet hemostasis. This study was done to find any relationship between the levels of thrombopoietin and the severity of disease in patients with aplastic anemia. Materials and Methods: Serum samples were collected from 52 patients with a confirmed diagnosis of aplastic anemia and 45 normal healthy blood donors of both sexes over a period of 2 years, and TPO was estimated by using commercially available TPO-specific-enzyme-linked immunosorbent assay. Results: The median TPO level of 1190 pg/ml (range 625-7651 pg/ml) in aplastic anemia patients was significantly higher than the median TPO level of 121.1 pg/ml (81.25-237.7 pg/ml) in normal healthy blood donors (P = 0.000). No significant difference was observed in TPO levels of male and female patients (P = 0.453). The median TPO concentrations observed in very severe aplastic anemia, severe aplastic anemia, and nonsevere aplastic anemia were 2765 pg/ml (range 625-6451 pg/ml), 1190 pg/ml (range 672.1-7651 pg/ml), and 1111.5 pg/ml (range 761.1-2289.2 pg/ml), respectively. TPO in patients of very severe aplastic anemia was significantly higher than patients of nonsevere aplastic anemia (P = 0.043), with no significant relation among rest of the groups. Discussion: TPO levels in aplastic anemia patients were significantly higher than in healthy blood donors; however, in aplastic anemia patients TPO levels were significantly higher only in patients with very severe disease. PMID:25722577

  1. Sickle Cell Anemia

    MedlinePlus

    Sickle cell anemia is a disease in which your body produces abnormally shaped red blood cells. The cells are shaped like ... normal, round red blood cells. This leads to anemia. The sickle cells also get stuck in blood ...

  2. Analysis of non-typeable Haemophilus influenzae in invasive disease reveals lack of the capsule locus.

    PubMed

    Lâm, T-T; Claus, H; Frosch, M; Vogel, U

    2016-01-01

    Among invasive Haemophilus influenzae, unencapsulated strains have largely surpassed the previously predominant serotype b (Hib) because of Hib vaccination. Isolates without the genomic capsule (cap) locus are designated non-typeable H. influenzae (NTHi). They are different from capsule-deficient variants that show deletion of the capsule transport gene bexA within the cap locus. The frequency of capsule-deficient variants in invasive disease is unknown. We analysed 783 unencapsulated invasive isolates collected over 5 years in Germany and found no single capsule-deficient isolate. Invasive unencapsulated strains in Germany were exclusively NTHi. A negative serotyping result by slide agglutination was therefore highly predictive for NTHi.

  3. COEXISTENCE OF ADDISON'S DISEASE AND PERNICIOUS ANEMIA: IS THE NEW CLASSIFICATION OF AUTOIMMUNE POLYGLANDULAR SYNDROME APPROPRIATE?

    PubMed

    Vrkljan, Ana Marija; Pašalić, Ante; Strinović, Mateja; Perić, Božidar; Kruljac, Ivan; Miroševć, Gorana

    2015-06-01

    A case of autoimmune polyglandular syndrome (APS) is presented. A 45-year-old man was admitted due to fatigue, malaise and inappetence. He had a history of primary hypothyroidism and was on levothyroxine substitution therapy. One year before, he was diagnosed with normocytic anemia and vitamin B12 deficiency, which was treated with vitamin B12 substitution therapy. Physical examination revealed hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed low morning cortisol and increased adrenocorticotropic hormone levels. Hence, the diagnosis of Addison's disease was established. Additional laboratory workup showed positive parietal cell antibodies. However, his vitamin B12 levels were increased due to vitamin B12 supplementation therapy, which was initiated earlier. Gastroscopy and histopathology of gastric mucosa confirmed atrophic gastritis. Based on prior low serum vitamin B12 levels, positive parietal cell antibodies and atrophic gastritis, the patient was diagnosed with pernicious anemia. Hydrocortisone supplementation therapy was administered and titrated according to urinary-free cortisol levels. Electrolyte disbalance and red blood cell count were normalized. This case report demonstrates rather unique features of pernicious anemia in a patient with Addison's disease. It also highlights the link between type II and type III APS. Not only do they share the same etiological factors, but also overlap in pathophysiological and clinical characteristics. This case report favors older classification of APS, which consolidates all endocrine and other organ-specific autoimmune diseases into one category. This is important since it might help avoid pitfalls in the diagnosis and treatment of patients with APS.

  4. Characterization of the anemia of inflammatory disease in cats with abscesses, pyothorax, or fat necrosis.

    PubMed

    Ottenjann, Mareike; Weingart, Christiane; Arndt, Gisela; Kohn, Barbara

    2006-01-01

    The purpose of this study was to describe the anemia of inflammatory disease (AID) in cats with naturally-occurring inflammatory diseases, such as abscesses (n = 12), pyothorax (n = 6), and fat necrosis (n = 3). Exclusion criteria were positive FeLV/FIV tests, neoplasia, nephro-, hepato- or endocrinopathies, and blood loss anemia. CBC, clinical biochemistry, measurements of serum erythropoietin, iron, total iron-binding capacity (TIBC), ferritin, acute phase proteins, erythrocytic osmotic fragility (OF), and Coombs' tests were performed. A decrease in hematocrit of 1-28% (median, 10%) occurred within 3-16 days (median, 8 days). The anemia was mild (n = 11), moderate (n = 8), or severe (n = 2). In most cases it was normocytic normochromic, non-regenerative (n = 18), or mildly regenerative (n = 3). Sixteen cats had leukocytosis and 5 mild hyperbilirubinemia. The Coombs' test results were negative for 8 cats and positive for 1 cat. OF was increased in 2 out of 14 cats. Hypoalbuminemia (n = 18) and hyperglobulinemia (n = 16) resulted in a lowered albumin/globulin-ratio in 19 cats. Iron and TIBC were low in 2/19 and 6 /19 cats, respectively. The ferritin concentrations were normal in 7 cats and increased in 12 cats. The acute phase proteins alpha1-acid-glycoprotein and haptoglobin were increased in 14/14 and 13/14 cats, respectively. Erythropoietin was normal (n = 4), mildly increased (n = 7) or severely increased (1). Two cats were euthanized due to their underlying disease, 3 cats needed blood transfusions. AID in cats is usually mild to moderate, non-regenerative, and normocytic normochromic. It can be clinically relevant causing severe and transfusion-dependent anemia. AID seems to be multifactorial with evidence of iron sequestration, decreased RBC survival, and insufficient erythropoietin production and bone marrow response. Specific and supportive therapy, including transfusions, can reverse these processes.

  5. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.

    PubMed

    Khor, Chiea Chuen; Davila, Sonia; Breunis, Willemijn B; Lee, Yi-Ching; Shimizu, Chisato; Wright, Victoria J; Yeung, Rae S M; Tan, Dennis E K; Sim, Kar Seng; Wang, Jie Jin; Wong, Tien Yin; Pang, Junxiong; Mitchell, Paul; Cimaz, Rolando; Dahdah, Nagib; Cheung, Yiu-Fai; Huang, Guo-Ying; Yang, Wanling; Park, In-Sook; Lee, Jong-Keuk; Wu, Jer-Yuarn; Levin, Michael; Burns, Jane C; Burgner, David; Kuijpers, Taco W; Hibberd, Martin L

    2011-11-13

    Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.

  6. Anemia in pregnancy.

    PubMed

    Horowitz, Kari M; Ingardia, Charles J; Borgida, Adam F

    2013-06-01

    Hemodynamic changes occur in pregnancy to prepare for expected blood loss at delivery. Physiologic anemia occurs in pregnancy because plasma volume increases more quickly than red cell mass. Anemia is most commonly classified as microcytic, normocytic, or macrocytic. Iron deficiency anemia accounts for 75% of all anemias in pregnancy. Oral iron supplementation is the recommended treatment of iron deficiency anemia in pregnancy. Parenteral iron and erythropoietin can also be used in severe or refractory cases. Outcomes and treatments for other forms of inherited and acquired anemias in pregnancy vary by disease, and include nutritional supplementation, corticosteroids, supportive transfusions, and splenectomy.

  7. Estimating locus heterogeneity in autosomal dominant polycystic kidney disease (ADPKD) in the Spanish population.

    PubMed Central

    Peral, B; San Millán, J L; Hernández, C; Valero, A; Lathrop, G M; Beckmann, J S; Moreno, F

    1993-01-01

    Although most mutations causing ADPKD in European populations have been mapped to the PKD1 locus on chromosome 16, some of them appear to be unlinked to this locus. To evaluate the incidence of unlinked mutations in Spain we have typed 31 Spanish families from different geographical sites for six closely linked DNA polymorphic marker loci flanking PKD1 detected by probes D16S85, D16S21, D16S259, D16S125, D16S246, and D16S80. Multilocus linkage analysis indicated that in 26 families the disease resulted from PKD1 mutations, whereas in three families it resulted from mutations in a locus other than PKD1. The two other families were not informative. Using the HOMOG test, the incidence of the PKD1 linked mutations in Spain is 85%. Multipoint linkage analysis in the 26 PKD1 families showed that the disease locus lies in the interval between D16S259(pGGG1) and D16S125(26.6). PMID:7905535

  8. Anemia in older persons.

    PubMed

    Bross, Michael H; Soch, Kathleen; Smith-Knuppel, Teresa

    2010-09-01

    Anemia in older persons is commonly overlooked despite mounting evidence that low hemoglobin levels are a significant marker of physiologic decline. Using the World Health Organization definition of anemia (hemoglobin level less than 13 g per dL [130 g per L] in men and less than 12 g per dL [120 g per L] in women), more than 10 percent of persons older than 65 years are anemic. The prevalence increases with age, approaching 50 percent in chronically ill patients living in nursing homes. There is increasing evidence that even mild anemia is associated with increased morbidity and mortality. Anemia warrants evaluation in all older persons, except those at the end of life or who decline interventions. About one third of persons have anemia secondary to a nutritional deficiency, one third have anemia caused by chronic inflammation or chronic kidney disease, and one third have unexplained anemia. Nutritional anemia is effectively treated with vitamin or iron replacement. Iron deficiency anemia often is caused by gastrointestinal bleeding and requires further investigation in most patients. Anemia of chronic inflammation or chronic kidney disease may respond to treatment of the underlying disease and selective use of erythropoiesis-stimulating agents. The treatment of unexplained anemia is difficult, and there is little evidence that treatment decreases morbidity and mortality, or improves quality of life. Occasionally, anemia may be caused by less common but potentially treatable conditions, such as autoimmune hemolytic anemia, malignancy, or myelodysplastic syndrome.

  9. Tomato mutants altered in bacterial disease resistance provide evidence for a new locus controlling pathogen recognition.

    PubMed Central

    Salmeron, J M; Barker, S J; Carland, F M; Mehta, A Y; Staskawicz, B J

    1994-01-01

    We have employed a genetic approach to study the resistance of tomato to the phytopathogenic bacterium Pseudomonas syringae pv tomato. Resistance to P. s. tomato depends upon expression of the Pto locus in tomato, which encodes a protein with similarity to serine/threonine protein kinases and recognizes pathogen strains expressing the avirulence gene avrPto. Eleven tomato mutants were isolated with altered resistance to P. s. tomato strains expressing avrPto. We identified mutations both in the Pto resistance locus and in a new locus designated Prf (for Pseudomonas resistance and fenthion sensitivity). The genetic approach allowed us to dissect the roles of these loci in signal transduction in response to pathogen attack. Lines carrying mutations in the Pto locus vary 200-fold in the degree to which they are susceptible to P. s. tomato strains expressing avrPto. The pto mutants retain sensitivity to the organophosphate insecticide fenthion; this trait segregates with Pto in genetic crosses. This result suggested that contrary to previous hypotheses, the Pto locus controls pathogen recognition but not fenthion sensitivity. Interestingly, mutations in the prf locus result in both complete susceptibility to P. s. tomato and insensitivity to fenthion, suggesting that Prf plays a role in tomato signaling in response to both pathogen elicitors and fenthion. Because pto and prf mutations do not alter recognition of Xanthomonas campestris strains expressing avrBsP, an avirulence gene recognized by all tested tomato cultivars, Prf does not play a general role in disease resistance but possibly functions specifically in resistance against P. s. tomato. Genetic analysis of F2 populations from crosses of pto and prf homozygotes indicated that the Pto and Prf loci are tightly linked. PMID:7911348

  10. A Study of Human Leukocyte D Locus Related Antigens in Graves' Disease

    PubMed Central

    Farid, Nadir R.; Sampson, Laura; Noel, Elke P.; Barnard, John M.; Mandeville, Robert; Larsen, Bodil; Marshall, William H.; Carter, Nicholas D.

    1979-01-01

    An association between Graves' disease and the human leukocyte antigen (HLA) system has previously been reported. The disease was more strongly associated with the HLA D locus antigen Dw3 than with HLA B8. Products of the HLA D locus are determined by the interaction of test cells with standard typing lymphocytes, a technically difficult procedure. Recently, it has been possible to type serologically for D locus related (DRw) specificities on peripheral bone marrow-derived (B) lymphocytes. Blood B lymphocytes from 50 unrelated controls and 41 patients with Graves' disease were typed for seven HLA DRw specificities. 28 patients with Graves' disease (68%) were positive for DRw3, in contrast to 14 controls (28%); whereas only 21 patients (50%) were HLA B8 positive, compared with 13 (26%) controls. Thus, positivity for DRw3 afforded a relative risk for Graves' disease of 5.5, whereas that for HLA B8 amounted to 3.0. Additionally, a family with multiple cases of Graves' disease in which the disease was previously shown to be inherited with the haplotype, was linked to DRw2, which suggests that the susceptibility to the disease was inherited in association with that antigen. Two HLA B/glyoxalase recombination events were observed in this family; in both instances HLA DRw followed HLA B. This study thus demonstrates that the disease susceptibility gene for Graves' disease is in strong linkage disequilibrium with DRw3; however, it may be associated with other DRw specificities and inherited within family units in association with them. PMID:105012

  11. [Diagnosis and therapy of anemia in chronic diseases].

    PubMed

    Scudla, V; Adam, Z; Scudlová, M

    2001-06-01

    The article deals with contemporary views on anaemia associated with chronic diseases. The authors present the definition of this nosological unit, draw attention to its high incidence in clinical practice and fact that it is frequently mistaken for iron deficiency anaemia. The authors submit a review of the most frequent diseases which cause the development of this type of anaemia and analyze the role of activation of the system of cellular immunity, the monocyte-macrophage system, agents of the cytokine network in inhibition of proliferation and differentiation of erythroid precursors, reduced production of endogenous erythropoietin with a reduced sensitivity of erythroid progenitor cells to its action and impaired iron homeostasis and inhibition of its reutilization. Special attention is devoted to diagnostic and differential diagnostic criteria in relation to other types of anaemia caused by impaired haeme synthesis and some secondary multifactorially conditioned types of anaemia. More detailed attention is paid to the diagnostic value of evaluating serum levels of soluble transferrin receptors and explanation of the asset of calculation of the transferrin receptor/ferririn index as a sensitive indicator of latent sideropenia as well as the Fe-absorption test using low oral iron doses. Part of the paper is also an account of contemporary possibilities of treatment including the use of the recombinant form of human erythropoietin, and attention is drawn to the unsuitability and pitfalls of iron therapy in this type of anaemia.

  12. The relationship between anemia, liver disease, and hepcidin levels in hemodialysis patients with hepatitis.

    PubMed

    Zumrutdal, A; Sezgin, N

    2012-11-01

    We investigated the role of hepcidin in ameliorating anemia in hemodialysis patients with hepatitis. A total of 72 hemodialysis patients with hepatitis were classified according to their requirement of erythropoietin (EPO). Anemia parameters, C-reactive protein (CRP), and biochemical measurements were recorded along with the hepcidin. The number of patients receiving no EPO was higher among patients with liver disease when compared with those without liver disease (P = 0.002). The mean hepcidin levels of the patients who did not receive EPO did not differ statistically from those of the patients who received the maximum dose (P = 0.5). The hepcidin levels of patients with liver disease who received no EPO were lower compared to those patients without liver disease who received the maximum dose (P = 0.04). There was a positive correlation between hepcidin and mean platelet levels (r = 0.26, P = 0.027) and annual intravenous iron dose (r = 0.31, P = 0.007). In hemodialysis patients with hepatitis, liver disease may be one of the factors affecting erythropiesis, related with decreased hepcidin levels and iron hemostasis. Further studies are needed to verify these associations.

  13. [Complementary treatment of acute heart failure in patients with diabetes, chronic obstructive pulmonary disease or anemia].

    PubMed

    Carrasco Sánchez, Francisco Javier; Recio Iglesias, Jesús; Grau Amorós, Jordi

    2014-03-01

    Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF.

  14. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia.

    PubMed

    Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Bronze-da-Rocha, Elsa; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

    2015-12-25

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.

  15. Chromosome substitution strain assessment of a Huntington's disease modifier locus.

    PubMed

    Ramos, Eliana Marisa; Kovalenko, Marina; Guide, Jolene R; St Claire, Jason; Gillis, Tammy; Mysore, Jayalakshmi S; Sequeiros, Jorge; Wheeler, Vanessa C; Alonso, Isabel; MacDonald, Marcy E

    2015-04-01

    Huntington's disease (HD) is a dominant neurodegenerative disorder that is due to expansion of an unstable HTT CAG repeat for which genome-wide genetic scans are now revealing chromosome regions that contain disease-modifying genes. We have explored a novel human-mouse cross-species functional prioritisation approach, by evaluating the HD modifier 6q23-24 linkage interval. This unbiased strategy employs C57BL/6J (B6J) Hdh(Q111) knock-in mice, replicates of the HD mutation, and the C57BL/6J-chr10(A/J)/NaJ chromosome substitution strain (CSS10), in which only chromosome 10 (chr10), in synteny with the human 6q23-24 region, is derived from the A/J (AJ) strain. Crosses were performed to assess the possibility of dominantly acting chr10 AJ-B6J variants of strong effect that may modulate CAG-dependent Hdh(Q111/+) phenotypes. Testing of F1 progeny confirmed that a single AJ chromosome had a significant effect on the rate of body weight gain and in Hdh(Q111) mice the AJ chromosome was associated subtle alterations in somatic CAG instability in the liver and the formation of intra-nuclear inclusions, as well as DARPP-32 levels, in the striatum. These findings in relatively small cohorts are suggestive of dominant chr10 AJ-B6 variants that may modify effects of the CAG expansion, and encourage a larger study with CSS10 and sub-strains. This cross-species approach may therefore be suited to functional in vivo prioritisation of genomic regions harbouring genes that can modify the early effects of the HD mutation.

  16. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    SciTech Connect

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  17. Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease: A nested case-control study

    PubMed Central

    Loutradis, Charalampos; Skodra, Alexandra; Georgianos, Panagiotis; Tolika, Panagiota; Alexandrou, Dimitris; Avdelidou, Afroditi; Sarafidis, Pantelis A

    2016-01-01

    AIM: To compare anemia prevalence between matched chronic kidney disease (CKD) patients with and without diabetes mellitus (DM) and to assess factors associated with anemia development. METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate (eGFR). Prevalence of anemia (hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia. RESULTS: The total prevalence of anemia was higher in diabetics (47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3 (53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a (60.4% vs 26.4%, P < 0.001), whereas it was non-significantly higher in Stage 4 (61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM (OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4 (Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron (OR = 0.976, 95%CI: 0.968-0.985 per mg/dL increase) were independently associated with anemia. CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts. PMID:27458564

  18. A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

    PubMed Central

    Kniazeva, M; Chiang, M F; Morgan, B; Anduze, A L; Zack, D J; Han, M; Zhang, K

    1999-01-01

    Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4. PMID:10205271

  19. Sickle cell anemia, the first molecular disease: overview of molecular etiology, pathophysiology, and therapeutic approaches.

    PubMed

    Steinberg, Martin H

    2008-12-25

    The root cause of sickle cell disease is a single beta-globin gene mutation coding for the sickle beta-hemoglobin chain. Sickle hemoglobin tetramers polymerize when deoxygenated, damaging the sickle erythrocyte. A multifaceted pathophysiology, triggered by erythrocyte injury induced by the sickle hemoglobin polymer, and encompassing more general cellular and tissue damage caused by hypoxia, oxidant damage, inflammation, abnormal intracellular interactions, and reduced nitric oxide bioavailability, sets off the events recognized clinically as sickle cell disease. This disease is a group of related disorders where sickle hemoglobin is the principal hemoglobin species. All have varying degrees of chronic hemolytic anemia, vasculopathy, vasoocclusive disease, acute and chronic organ damage, and shortened life span. Its complex pathophysiology, of which we have a reasonable understanding, provides multiple loci for potential therapeutic intervention.

  20. Lafora disease is not linked to the Unverricht-Lundborg locus

    SciTech Connect

    Labauge, P.; Beck, C.; Bellet, H.; Baldy-Moulinier, M.; Malafosse, A.

    1995-02-27

    Lafora disease and Unverricht-Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht-Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North-African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht-Lundborg disease may be facilitated by molecular genetic analysis. 16 refs., 2 figs., 2 tabs.

  1. Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease.

    PubMed

    Vlagopoulos, Panagiotis T; Tighiouart, Hocine; Weiner, Daniel E; Griffith, John; Pettitt, Dan; Salem, Deeb N; Levey, Andrew S; Sarnak, Mark J

    2005-11-01

    Anemia is a potential nontraditional risk factor for cardiovascular disease (CVD). This study evaluated whether anemia is a risk factor for adverse outcomes in people with diabetes and whether the risk is modified by the presence of chronic kidney disease (CKD). Persons with diabetes from four community-based studies were pooled: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Anemia was defined as a hematocrit <36% in women and <39% in men. CKD was defined as an estimated GFR of 15 to 60 ml/min per 1.73 m(2). Study outcomes included a composite of myocardial infarction (MI)/fatal coronary heart disease (CHD)/stroke/death and each outcome separately. Cox regression analysis was used to study the effect of anemia on the risk for outcomes after adjustment for potential confounders. The study population included 3015 individuals: 30.4% were black, 51.6% were women, 8.1% had anemia, and 13.8% had CKD. Median follow-up was 8.6 yr. There were 1215 composite events, 600 MI/fatal CHD outcomes, 300 strokes, and 857 deaths. In a model with a CKD-anemia interaction term, anemia was associated with the following hazard ratios (95% confidence intervals) in patients with CKD: 1.70 (1.24 to 2.34) for the composite outcome, 1.64 (1.03 to 2.61) for MI/fatal CHD, 1.81 (0.99 to 3.29) for stroke, and 1.88 (1.33 to 2.66) for all-cause mortality. Anemia was not a risk factor for any outcome in those without CKD (P > 0.2 for all outcomes). In persons with diabetes, anemia is primarily a risk factor for adverse outcomes in those who also have CKD.

  2. Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2014.

    PubMed

    Visconte, Valeria; Lindsley, R Coleman; Berlyne, Deborah

    2015-01-01

    Bone marrow failure syndromes (BMFS) are characterized by a failure of the hematopoietic stem cells to produce adequate blood cells, resulting in either cytopenia (defect in one or more blood cell lineages) or pancytopenia (defect in all blood cell lineages). BMFS can be inherited or acquired. The pathogenesis of these diseases is very heterogeneous. Research efforts have been made all over the world to improve the basic knowledge of these diseases. The Aplastic Anemia and MDS International Foundation (AA&MDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize novel scientific discoveries in several BMFS that were presented at the 4th International Bone Marrow Failure Disease Scientific Symposium 2014 that AA&MDSIF sponsored on March 27-28, 2014, in Rockville, MD.

  3. Aplastic anemia.

    PubMed

    Usuki, Kensuke

    Treatments of aplastic anemia are comprised of supportive therapy and aplastic anemia-specific therapy aimed at restoring hematopoiesis. Supportive therapies include transfusion, G-CSF, and the administration of iron chelation agents, as well as dealing specifically with individual symptoms. Aplastic anemia-specific treatments given with the aim of achieving hematopoietic recovery include immunosuppressive therapy, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although transplantation provides complete recovery of hematopoiesis (cure), there is a risk of death due to transplant-related complications. The most effective immunosuppressive therapy is a combination of anti-thymocyte globulin and cyclosporine. This treatment is also effective against the secondary, drug-induced and hepatitis-associated forms of aplastic anemia. In the management of aplastic anemia, a treatment is selected from among these options depending on the disease severity and the age of the individual case. The thrombopoietin receptor agonist eltrombopag appears to be effective and to provide tri-lineage recovery of hematopoiesis in some cases. Indications for its use are expected to expand in Japan.

  4. Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson's Disease Locus.

    PubMed

    Labbé, Catherine; Ogaki, Kotaro; Lorenzo-Betancor, Oswaldo; Carrasquillo, Minerva M; Heckman, Michael G; McCarthy, Allan; Soto-Ortolaza, Alexandra I; Walton, Ronald L; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Dickson, Dennis W; Uitti, Ryan J; Wszolek, Zbigniew K; Ross, Owen A

    2015-01-01

    Genome-wide association studies (GWAS) in Parkinson's disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11-1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD.

  5. Analysis of human chromosome 21 for a locus conferring susceptibility to Hirschsprung Disease

    SciTech Connect

    Bolk, S.; Duggan, D.J.; Chakravarti, A.

    1994-09-01

    It has been estimated that approximately 5% of patients diagnosed with Hirschsprung disease (HSCR), or aganglionic megacolon, have trisomy 21. Since the incidence of Hirschsprung disease is 1/5000 live births and the incidence of trisomy 21 is approximately 1/1000 live births, the observed occurrence of HSCR in trisomy 21 is fifty times higher than expected. We propose that at least one locus on chromosome 21 predisposes to HSCR. Although at fifty times elevated risk, only 1% of Down Syndrome cases have HSCR. Thus additional genes or genetic events are necessary for HSCR to manifest in patients with trisomy 21. Based on segregation analysis, Badner et al. postulated that recessive genes may be responsible for up to 80% of HSCR. We postulate that at least one such gene is on chromosome 21 and increased homozygosity for common recessive HSCR mutations may be one cause for the elevated risk of HSCR in cases of trisomy 21. To map such a chromosome 21 locus, we are searching for segments of human chromosome 21 which are identical by descent from the parent in whom non-disjunction occurred. These segments will arise either from meiosis I (followed by a crossover between the centromere and the locus) or from meiosis II (followed by no crossovers). Nine nuclear families with a proband diagnosed with HSCR and Down Syndrome have been genotyped for 18 microsatellite markers spanning human chromosome 21q. In all nine cases analyzed thus far, trisomy 21 resulted from maternal non-disjunction at meiosis I. At this point no single IBD region is apparent. Therefore, additional families are being ascertained and additional markers at high density are being genotyped to map the HSCR locus.

  6. Aplastic Anemia & MDS International Foundation

    MedlinePlus

    ... Menu Donate I'm Like You. "The Aplastic Anemia and MDS International Foundation is helping patients like ... cope with bone marrow failure disease." Diseases Aplastic Anemia Myelodysplastic Syndromes (MDS) Paroxysmal Nocturnal Hemoglobinuria (PNH) Related ...

  7. Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

    SciTech Connect

    Rubinstein, W.S.; Wenger, S.L.; Hoffman, R.M.

    1997-03-31

    We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderately severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,X-Y with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. 49 refs., 2 figs., 1 tab.

  8. Epidural anesthesia for laparoscopic cholecystectomy in a patient with sickle cell anemia, beta thalassemia, and Crohn's disease -A case report-

    PubMed Central

    Özlü, Onur

    2012-01-01

    A 37-year-old woman diagnosed with sickle cell anemia (SCA), beta (+) thalassemia, Crohn's disease, and liver dysfunction was scheduled for laparoscopic cholecystectomy (LC) due to acute cholecystitis with gall bladder. Regional anesthesia was performed. An epidural catheter was inserted into the 9-10 thoracal epidural space and then 15 ml of 0.5% bupivacaine was injected through the catheter. The level of sensorial analgesia tested with pinprick test reached up to T4. Here we describe the first case of the combination of sickle cell anemia (SCA), beta (+) thalassemia, and Crohn's disease successful anesthetic management with attention to hemodynamics, particularly with regards to liver dysfunction. PMID:23115690

  9. Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients

    PubMed Central

    Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

    2016-01-01

    Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD’s acute inflammatory phase. PMID:27187366

  10. Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients.

    PubMed

    Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

    2016-05-12

    Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD's acute inflammatory phase.

  11. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model

    PubMed Central

    Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

    2017-01-01

    Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. PMID:28143953

  12. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

    PubMed

    Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

    2017-02-01

    Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis.

  13. [Maternal Crohn's disease-related vitamin B12 deficient megaloblastic anemia in an infant].

    PubMed

    Ohyama, Wataru; Yamaoka, Masayoshi; Yokoi, Kentaro; Iwahashi, Megumi; Inage, Yuka; Arihiro, Seiji; Koganei, Kazutaka; Sugita, Akira; Ida, Hiroyuki; Akiyama, Masaharu

    2016-01-01

    We report an 11-month-old breast-fed boy with feeding difficulties, lethargy, and developmental delay. Blood examination showed pancytopenia and decreased serum levels of vitamin B12. Anisocytosis and poikilocytes were detected in his peripheral blood, and increased megaloblastosis without leukemic cells was detected in his bone marrow. After the diagnosis of megaloblastic anemia due to vitamin B12 deficiency, symptoms were improved by vitamin B12 administration. Further investigation of the mother identified Crohn's disease and suggested that the supply of vitamin B12 from the mother to the infant, via the placenta during pregnancy and via breast milk after birth, was decreased due to impaired absorption of vitamin B12 in the mother's small intestine. Magnetic resonance imaging of the boy's brain on admission showed cerebral cortex atrophy which had improved by the age of 1 year and 10 months after vitamin B12 treatment, though developmental delay was still evident at the age of 3 years. Infantile vitamin B12 deficiency often presents with nonspecific manifestations, such as developmental delay and failure to thrive, in addition to anemia and is thus not easily diagnosed. To prevent severe neurological sequelae, this condition must be rapidly diagnosed, because a prolonged duration increases the risk of permanent disabilities.

  14. Anemia of inflammation.

    PubMed

    Nemeth, Elizabeta; Ganz, Tomas

    2014-08-01

    Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. It is diagnosed when serum iron concentrations are low despite adequate iron stores, as evidenced by serum ferritin that is not low. In the setting of inflammation, it may be difficult to differentiate AI from iron deficiency anemia, and the 2 conditions may coexist. Treatment should focus on the underlying disease. Recent advances in molecular understanding of AI are stimulating the development of new pathophysiologically targeted experimental therapies.

  15. CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology.

    PubMed

    Bradshaw, Elizabeth M; Chibnik, Lori B; Keenan, Brendan T; Ottoboni, Linda; Raj, Towfique; Tang, Anna; Rosenkrantz, Laura L; Imboywa, Selina; Lee, Michelle; Von Korff, Alina; Morris, Martha C; Evans, Denis A; Johnson, Keith; Sperling, Reisa A; Schneider, Julie A; Bennett, David A; De Jager, Philip L

    2013-07-01

    In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444(C) risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P(joint) = 1.3 × 10(-13)) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

  16. [Sideroblastic anemias].

    PubMed

    Matthes, T

    2006-01-01

    Sideroblastic anemias are a heterogenous group of disorders characterized by the presence of sideroblasts in the bone marrow aspirate. Current classification schemes distinguish between diseases of the heme synthesis pathway and diseases of other mitochondrial pathways which can either be of primary origin (defects in mitochondrial DNA) or of secondary origin (defects in nuclear DNA). Although several distinct hereditary forms exist, sideroblastic anemias are most frequently acquired diseases and belong to the group of myelodysplastic syndromes with the propensity to develop into overt leukemia. Treatment is mainly supportive (vitamins, blood transfusions, cytokines) and only rarely are bone marrow transplantations performed. The molecular defects of a few hereditary forms have already been elucidated, but the genes involved in the acquired forms are still largely unknown.

  17. [Iron dysregulation and anemias].

    PubMed

    Ikuta, Katsuya

    2015-10-01

    Most iron in the body is utilized as a component of hemoglobin that delivers oxygen to the entire body. Under normal conditions, the iron balance is tightly regulated. However, iron dysregulation does occasionally occur; total iron content reductions cause iron deficiency anemia and overexpression of the iron regulatory peptide hepcidin disturbs iron utilization resulting in anemia of chronic disease. Conversely, the presence of anemia may ultimately lead to iron overload; for example, thalassemia, a common hereditary anemia worldwide, often requires transfusion, but long-term transfusions cause iron accumulation that leads to organ damage and other poor outcomes. On the other hand, there is a possibility that iron overload itself can cause anemia; iron chelation therapy for the post-transfusion iron overload observed in myelodysplastic syndrome or aplastic anemia improves dependency on transfusions in some cases. These observations reflect the extremely close relationship between anemias and iron metabolism.

  18. Iron Deficiency Anemia in Relation to Respiratory Disease and Social Behaviors In Low-Income Infants in France.

    ERIC Educational Resources Information Center

    Honig, Alice Sterling

    1993-01-01

    Examined a sample of 177 infants (age 9 through 12 months) with iron deficiency anemia (IDA) from low-income French, African, and North African Muslim families in Paris. Found a higher than normal incidence of otitis media and respiratory diseases such as bronchitis among the infants. Also examined the relationship between infant IDA and child…

  19. Intestine-specific Disruption of Hypoxia-inducible Factor (HIF)-2α Improves Anemia in Sickle Cell Disease.

    PubMed

    Das, Nupur; Xie, Liwei; Ramakrishnan, Sadeesh K; Campbell, Andrew; Rivella, Stefano; Shah, Yatrik M

    2015-09-25

    Sickle cell disease (SCD) is caused by genetic defects in the β-globin chain. SCD is a frequently inherited blood disorder, and sickle cell anemia is a common type of hemoglobinopathy. During anemia, the hypoxic response via the transcription factor hypoxia-inducible factor (HIF)-2α is highly activated in the intestine and is essential in iron absorption. Intestinal disruption of HIF-2α protects against tissue iron accumulation in iron overload anemias. However, the role of intestinal HIF-2α in regulating anemia in SCD is currently not known. Here we show that in mouse models of SCD, disruption of intestinal HIF-2α significantly decreased tissue iron accumulation. This was attributed to a decrease in intestinal iron absorptive genes, which were highly induced in a mouse model of SCD. Interestingly, disruption of intestinal HIF-2α led to a robust improvement in anemia with an increase in RBC, hemoglobin, and hematocrit. This was attributed to improvement in RBC survival, hemolysis, and insufficient erythropoiesis, which is evident from a significant decrease in serum bilirubin, reticulocyte counts, and serum erythropoietin following intestinal HIF-2α disruption. These data suggest that targeting intestinal HIF-2α has a significant therapeutic potential in SCD pathophysiology.

  20. ATP5H/KCTD2 locus is associated with Alzheimer's disease risk

    PubMed Central

    Boada, M; Antúnez, C; Ramírez-Lorca, R; DeStefano, A L; González-Pérez, A; Gayán, J; López-Arrieta, J; Ikram, M A; Hernández, I; Marín, J; Galán, J J; Bis, J C; Mauleón, A; Rosende-Roca, M; Moreno-Rey, C; Gudnasson, V; Morón, F J; Velasco, J; Carrasco, J M; Alegret, M; Espinosa, A; Vinyes, G; Lafuente, A; Vargas, L; Fitzpatrick, A L; Launer, L J; Sáez, M E; Vázquez, E; Becker, J T; López, O L; Serrano-Ríos, M; Tárraga, L; van Duijn, C M; Real, L M; Seshadri, S; Ruiz, A

    2014-01-01

    To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10−6 were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10−7 in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10−9). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation. PMID:23857120

  1. Unusual Anemias.

    PubMed

    Daughety, Molly Maddock; DeLoughery, Thomas G

    2017-03-01

    Many processes lead to anemia. This review covers anemias that are less commonly encountered in the United States. These anemias include hemoglobin defects like thalassemia, bone marrow failure syndromes like aplastic anemia and pure red cell aplasia, and hemolytic processes such as paroxysmal nocturnal hemoglobinuria. The pathogenesis, diagnostic workup, and treatment of these rare anemias are reviewed.

  2. Positional cloning of the chromosome 14 Alzheimer`s disease locus

    SciTech Connect

    Clark, R.F.; Korenblat, K.M.; Goate, A.M.

    1994-09-01

    Genetic linkage analysis had indicated a locus for familial early-onset Alzheimer`s disease (FAD) on chromosome 14 at q24.3. The FAD locus has been shown previously to lie between the dinucleotide markers D14S61 and D14S63, a genetic distance of approximately 13 cM. We are currently attempting to identify the gene using a positional cloning strategy. The first step towards the isolation and characterization of this locus was the construction of an overlapping YAC contig covering the entire region. Over forty YACs which map to this region have been isolated from the St. Louis and CEPH libraries by a combination of YAC end sequence walking and sequence tagged site mapping. Our contig fully spans the complete domain, encompassing all genetic markers non-recombinant with FAD (i.e. D14S76, D14S43, D14S71, D14S77) and the two nearest flanking FAD-recombinant markers. With restriction mapping of the domain, we can determine the exact size of the region. As a second step, the YACs in this contig are currently being inspected for expressed sequences by exon trapping, initially on those YACs known to be nonchimeric. We have currently made exon-trapped libraries from YACs that have the markers D14S76 and D14S43. Sequence analysis of these libraries indicates that a trapped exon is identified on average for each 30 kb of YAC DNA. The trapped exons are being screened to identify likely candidate genes, which will be examined for mutations in FAD families.

  3. A locus of group A Streptococcus involved in invasive disease and DNA transfer.

    PubMed

    Hidalgo-Grass, Carlos; Ravins, Miriam; Dan-Goor, Mary; Jaffe, Joseph; Moses, Allon E; Hanski, Emanuel

    2002-10-01

    Group A streptococcus (GAS) causes diseases ranging from benign to severe infections such as necrotizing fasciitis (NF). The reasons for the differences in severity of streptococcal infections are unexplained. We developed the polymorphic-tag-lengths-transposon-mutagenesis (PTTM) method to identify virulence genes in vivo. We applied PTTM on an emm14 strain isolated from a patient with NF and screened for mutants of decreased virulence, using a mouse model of human soft-tissue infection. A mutant that survived in the skin but was attenuated in its ability to reach the spleen and to cause a lethal infection was identified. The transposon was inserted into a small open reading frame (ORF) in a locus termed sil, streptococcal invasion locus. sil contains at least five genes (silA-E) and is highly homologous to the quorum-sensing competence regulons of Streptococcus pneumoniae. silA and silB encode a putative two-component system whereas silD and silE encode two putative ABC transporters. silC is a small ORF of unknown function preceded by a combox promoter. Insertion and deletion mutants of sil had a diminished lethality in the animal model. Virulence of a deletion mutant of silC was restored when injected together with the avirulent emm14-deletion mutant, but not when these mutants were injected into opposite flanks of a mouse. DNA transfer between these mutants occurred in vivo but could not account for the complementation of virulence. DNA exchange between the emm14-deletion mutant and mutants of sil occurred also in vitro, at a frequency of approximately 10-8 for a single antibiotic marker. Whereas silC and silD mutants exchanged markers with the emm14 mutant, silB mutant did not. Thus, we identified a novel locus, which controls GAS spreading into deeper tissues and could be involved in DNA transfer.

  4. Dihydrofolate Reductase Deficiency Due to a Homozygous DHFR Mutation Causes Megaloblastic Anemia and Cerebral Folate Deficiency Leading to Severe Neurologic Disease

    PubMed Central

    Cario, Holger; Smith, Desirée E.C.; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

    2011-01-01

    The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate. PMID:21310277

  5. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.

    PubMed

    Cario, Holger; Smith, Desirée E C; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

    2011-02-11

    The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate.

  6. A major effect quantitative trait locus for whirling disease resistance identified in rainbow trout (Oncorhynchus mykiss)

    PubMed Central

    Baerwald, M R; Petersen, J L; Hedrick, R P; Schisler, G J; May, B

    2011-01-01

    Whirling disease, caused by the pathogen Myxobolus cerebralis, leads to skeletal deformation, neurological impairment and under certain conditions, mortality of juvenile salmonid fishes. The disease has impacted the propagation and survival of many salmonid species over six continents, with particularly negative consequences for rainbow trout. To assess the genetic basis of whirling disease resistance in rainbow trout, genome-wide mapping was initiated using a large outbred F2 rainbow trout family (n=480) and results were confirmed in three additional outbred F2 families (n=96 per family). A single quantitative trait locus (QTL) region on chromosome Omy9 was identified in the large mapping family and confirmed in all additional families. This region explains 50–86% of the phenotypic variance across families. Therefore, these data establish that a single QTL region is capable of explaining a large percentage of the phenotypic variance contributing to whirling disease resistance. This is the first genetic region discovered that contributes directly to the whirling disease phenotype and the finding moves the field closer to a mechanistic understanding of resistance to this important disease of salmonid fish. PMID:21048672

  7. [Fatigue and anemia].

    PubMed

    Ivanova, K; Zeller, A

    2009-12-02

    We herein report on an 80-year old male patient with a history of muscle weakness, fatigue and weight loss since several months. Because of a pathologic synacthen test in combination with decreased levels of ACTH, we diagnosed a secondary chronic adrenal insufficiency. Because of a normochromic, normocytic, and hypo-proliferative anemia, bone marrow puncture was performed, showing an anemia of chronic disease. We initiated hydrocortisone and anemia and patients' symptoms were fully reconstituted.

  8. Oxidative stress during erythropoietin hyporesponsiveness anemia at end stage renal disease: Molecular and biochemical studies

    PubMed Central

    Khalil, Samar K.M.; Amer, H.A.; El Behairy, Adel M.; Warda, Mohamad

    2016-01-01

    Inflammation and oxidative stress are two faces of one coin in end stage renal disease patients (ESRD) on maintenance hemodialysis. Their interconnection induces anemia complicated with erythropoietin hyporesponsiveness. The biochemical bases behind the resistance to erythropoietin therapy with frequent hemoglobinemia, oxidative stress and iron status have not been fully understood. Here two equal groups (40 patients each) of responders and non-responders to recombinant human erythropoietin therapy (higher than 300 IU/kg/wk of epoetin) were investigated. Hematological and biochemical analyses of collected blood and serum samples were performed along with serum electrophoretic protein footprinting. The leukocytic DNA fragmentation was used to evaluate the degree of oxidative insult. The good responders showed lower erythrocyte malondialdehyde (E-MDA) level and less DNA fragmentation of circulating leukocytes than poor responders with elevated hemoglobin, albumin, A/G ratio, total iron, and ferritin levels. Contrariwise, lower erythrocyte superoxide dismutase (E-SOD) and catalase activities in EPO poor responder group were noticed. Neither other serum constituents nor electrophoretic protein pattern showed any difference between the two groups. There were higher levels of inflammatory markers, interleukin-6 (IL6) and C-reactive protein (CRP) in EPO poor responder than good responder. The negative correlations between Hb and both IL6 and CRP levels in the present data remotely indicate a positive correlation between inflammatory markers and severity of anemia. A direct correlation between Hb and antioxidant enzymes (E-SOD and catalase) was noticed, while inverse correlation with E-MDA was recorded. The study proved that oral supplementation of vitamin C to ESRD patients might mitigate the previously elevated serum MDA level in these patients. PMID:27222740

  9. Association between Vitamin D Deficiency and Anemia in Patients with End-Stage Renal Disease: A Cross-Sectional Study

    PubMed Central

    Kim, Yung Ly; Kim, Hyunwook; Kwon, Young Eun; Ryu, Dong-Ryeol; Lee, Mi Jung; Park, Kyung Sook; Ryu, Han Jak; Park, Jung Tak; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun

    2016-01-01

    Purpose Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. Materials and Methods We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. Results Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: β=0.263, p<0.001; age: β=0.122, p=0.010; ESA dose: β=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091–13.632; p=0.036). Conclusion 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients. PMID:27401647

  10. Hemolytic anemia

    MedlinePlus

    Anemia - hemolytic ... bones that helps form all blood cells. Hemolytic anemia occurs when the bone marrow isn't making ... destroyed. There are several possible causes of hemolytic anemia. Red blood cells may be destroyed due to: ...

  11. Hemolytic Anemia

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Hemolytic Anemia? Hemolytic anemia (HEE-moh-lit-ick uh-NEE-me-uh) ... blood cells to replace them. However, in hemolytic anemia, the bone marrow can't make red blood ...

  12. Distinguishing anemia and iron deficiency of heart failure: signal for severity of disease or unmet therapeutic need?

    PubMed

    Beavers, Craig J; Alburikan, Khalid A; Rodgers, Jo E; Dunn, Steven P; Reed, Brent N

    2014-07-01

    Despite advances in the management of heart failure (HF), quality of life and other outcomes remain suboptimal for many patients. Anemia and iron deficiency are comorbidities associated with adverse outcomes, although their pathophysiology in the setting of HF is not entirely understood. Anemia and iron deficiency may exist independently and may be a consequence of the systemic inflammatory state characterized by chronic HF. However, it is unclear whether serum hemoglobin concentrations and other hematologic parameters serve as markers for the severity of disease or represent novel therapeutic targets. Research in this area has focused primarily on therapies known to be effective for these conditions in other chronic disease states with similar pathophysiologic features (e.g., end-stage renal disease). Despite its many practical advantages, minimal evidence exists to support the use of oral iron supplementation in this setting. In contrast, intravenous iron has been the subject of several recent investigations, demonstrating improvements in both surrogate and clinical end points, although benefits seem to be the most substantial in patients with concomitant anemia. Erythropoietin-stimulating agents demonstrated early promise in retrospective analyses and small prospective trials, but their benefit was outweighed by a lack of improvement in clinical outcomes and an excess number of thromboembolic events in the largest trial of patients with anemia and HF to date. For acute symptomatic anemia, blood transfusion may be considered, although few trials have included patients with HF, and caution must be exerted in those who are hemodynamically unstable. Based on the currently available evidence, treatment of iron deficiency appears to confer benefit in patients with HF, whereas strategies aimed at improving hemoglobin alone do not. Included is a review of the pathophysiology of these conditions in the setting of HF, clinical trials evaluating pharmacologic therapy, and

  13. Homozygosity mapping of Fanconi anemia

    SciTech Connect

    Gschwend, M.; Botstein, D.; Kruglyak, L.

    1994-09-01

    Fanconi anemia (FA) is a rare, recessive, genetically heterogeneous disease characterized by progressive insufficiency of the bone marrow and increased cellular sensitivity to DNA crosslinking agents. Complementation tests among different FA cells have indicated the presence of at least 4 FA-causing genes. One of the genes, FACC, was identified by functional complementation but appears unlikely to account for many phenotypically indistinguishable FA caes. We have begun a linkage study of FA using {open_quotes}homozygosity mapping{close_quotes}, a method that involves genotyping with DNA markers on affected individuals whose parents are related. Because FA is a rare recessive disease, it is most likely that probands are homozygous by descent at the disease locus and, therefore, at nearby DNA markers. Although the probability that any given marker will be homozygous in an inbred individual is high, given markers with moderate heterozygosities, the chance that two unrelated inbred individuals will be homozygous at the same marker is considerably lower. By locating overlapping regions of homozygosity between different families we hope to identify genes that cause FA. Sixteen consanguineous non-FACC FA families from the International Fanconi Anemia Registry at Rockefeller University are under study. An efficient algorithm for data analysis was developed and incorporated into software that can quickly compute exact multipoint lod scores using all markers on an entire chromosome. At the time of this writing, 171 of 229 microsatellite markers spaced at 20 cM intervals across the genome have been analyzed.

  14. Congenital Hemolytic Anemia.

    PubMed

    Haley, Kristina

    2017-03-01

    Red blood cell (RBC) destruction can be secondary to intrinsic disorders of the RBC or to extrinsic causes. In the congenital hemolytic anemias, intrinsic RBC enzyme, RBC membrane, and hemoglobin disorders result in hemolysis. The typical clinical presentation is a patient with pallor, anemia, jaundice, and often splenomegaly. The laboratory features include anemia, hyperbilirubinemia, and reticulocytosis. For some congenital hemolytic anemias, splenectomy is curative. However, in other diseases, avoidance of drugs and toxins is the best therapy. Supportive care with transfusions are also mainstays of therapy. Chronic hemolysis often results in the formation of gallstones, and cholecystectomy is often indicated.

  15. Dynamics of disease resistance polymorphism at the Rpm1 locus of Arabidopsis.

    PubMed

    Stahl, E A; Dwyer, G; Mauricio, R; Kreitman, M; Bergelson, J

    1999-08-12

    The co-evolutionary 'arms race' is a widely accepted model for the evolution of host-pathogen interactions. This model predicts that variation for disease resistance will be transient, and that host populations generally will be monomorphic at disease-resistance (R-gene) loci. However, plant populations show considerable polymorphism at R-gene loci involved in pathogen recognition. Here we have tested the arms-race model in Arabidopsis thaliana by analysing sequences flanking Rpm1, a gene conferring the ability to recognize Pseudomonas pathogens carrying AvrRpm1 or AvrB. We reject the arms-race hypothesis: resistance and susceptibility alleles at this locus have co-existed for millions of years. To account for the age of alleles and the relative levels of polymorphism within allelic classes, we use coalescence theory to model the long-term accumulation of nucleotide polymorphism in the context of the short-term ecological dynamics of disease resistance. This analysis supports a 'trench warfare' hypothesis, in which advances and retreats of resistance-allele frequency maintain variation for disease resistance as a dynamic polymorphism.

  16. PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease

    PubMed Central

    Beecham, Gary W.; Dickson, Dennis W.; Scott, William K.; Martin, Eden R.; Schellenberg, Gerard; Nuytemans, Karen; Larson, Eric B.; Buxbaum, Joseph D.; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Hurtig, Howard I.; Mash, Deborah C.; Beach, Thomas G.; Troncoso, Juan C.; Pletnikova, Olga; Frosch, Matthew P.; Ghetti, Bernardino; Foroud, Tatiana M.; Honig, Lawrence S.; Marder, Karen; Vonsattel, Jean Paul; Goldman, Samuel M.; Vinters, Harry V.; Ross, Owen A.; Wszolek, Zbigniew K.; Wang, Liyong; Dykxhoorn, Derek M.; Pericak-Vance, Margaret A.; Montine, Thomas J.; Leverenz, James B.; Dawson, Ted M.

    2015-01-01

    Objective: To minimize pathologic heterogeneity in genetic studies of Parkinson disease (PD), the Autopsy-Confirmed Parkinson Disease Genetics Consortium conducted a genome-wide association study using both patients with neuropathologically confirmed PD and controls. Methods: Four hundred eighty-four cases and 1,145 controls met neuropathologic diagnostic criteria, were genotyped, and then imputed to 3,922,209 variants for genome-wide association study analysis. Results: A small region on chromosome 1 was strongly associated with PD (rs10788972; p = 6.2 × 10−8). The association peak lies within and very close to the maximum linkage peaks of 2 prior positive linkage studies defining the PARK10 locus. We demonstrate that rs10788972 is in strong linkage disequilibrium with rs914722, the single nucleotide polymorphism defining the PARK10 haplotype previously shown to be significantly associated with age at onset in PD. The region containing the PARK10 locus was significantly reduced from 10.6 megabases to 100 kilobases and contains 4 known genes: TCEANC2, TMEM59, miR-4781, and LDLRAD1. Conclusions: We confirm the association of a PARK10 haplotype with the risk of developing idiopathic PD. Furthermore, we significantly reduce the size of the PARK10 region. None of the candidate genes in the new PARK10 region have been previously implicated in the biology of PD, suggesting new areas of potential research. This study strongly suggests that reducing pathologic heterogeneity may enhance the application of genetic association studies to PD. PMID:25663231

  17. [Refractory anemias].

    PubMed

    Efira, A; Azerad, M-A

    2013-09-01

    Refractory anemia, also known as myelodysplastic syndromes, forms a group of clonal diseases characterized by cytopenias with mostly rich bone marrow. Preferentially reaching an older population, the prognosis depends on both comorbidities and characteristics of the disease, which have been grouped into a score established in 1997 ("IPSS = International Prognostic Scoring System") and revised in 2012 ("R-IPSS = Revised IPSS"). Overall survival and risk of transformation into acute nonlymphoblastic leukemia can now be estimated fairly accurately. Based on these characteristics, the treatment will be mainly supportive or will use several new molecules: growth factors, lenalidomide, 5-azacitidine, etc. A minority of patients may also benefit from allogeneic BMT or sometimes immunosuppressive therapy.

  18. High Dose Cyclophosphamide without Stem Cell Rescue in 207 Patients with Aplastic anemia and other Autoimmune Diseases

    PubMed Central

    DeZern, Amy E.; Petri, Michelle; Drachman, Daniel B.; Kerr, Doug; Hammond, Edward R.; Kowalski, Jeanne; Tsai, Hua-Ling; Loeb, David M.; Anhalt, Grant; Wigley, Fredrick; Jones, Richard J.; Brodsky, Robert A.

    2011-01-01

    High-dose cyclophosphamide has long been used an anticancer agent, a conditioning regimen for hematopoietic stem cell transplantation and as potent immunosuppressive agent in autoimmune diseases including aplastic anemia. High-dose cyclophosphamide is highly toxic to lymphocytes but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase, the major mechanism of cyclophosphamide inactivation. High dose cyclophosphamide therapy induces durable remissions in most patients with acquired aplastic anemia. Moreover, high-dose cyclophosphamide without hematopoietic stem cell rescue has shown activity in a variety of other severe autoimmune diseases. Here we review the history of cyclophosphamide as is applies to aplastic anemia (AA) and other autoimmune diseases. Included here are the historical data from early patients treated for AA as well as an observational retrospective study in a single tertiary care hospital. This latter component was designed to assess the safety and efficacy of high-dose cyclophosphamide therapy without stem cell rescue in patients with refractory autoimmune diseases. We analyzed fully the 140 patients with severe, progressive autoimmune diseases treated. All patients discussed here received cyclophosphamide, 50 mg/kg per day for 4 consecutive days. Response, relapse and overall survival were measured. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune modulating drugs. Relapse was defined as worsening disease activity and/or a requirement of an increase in dose of, or administration of new, immunosuppressive medications. Hematologic recovery occurred in all patients. The overall response rate of the was 95%, and 44% of those patients remain progression-free with a median follow up time of 36 (range 1–120) months for the 140 patients analyzed together. The overall actuarial and event free survival across all diseases at 60 months is 90.7% and 20

  19. Genetic variation at the PCSK9 locus, low density lipoproteins, response to pravastatin and coronary heart disease: results from PROSPER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucle...

  20. PoCos: Population Covering Locus Sets for Risk Assessment in Complex Diseases

    PubMed Central

    Koyutürk, Mehmet

    2016-01-01

    Susceptibility loci identified by GWAS generally account for a limited fraction of heritability. Predictive models based on identified loci also have modest success in risk assessment and therefore are of limited practical use. Many methods have been developed to overcome these limitations by incorporating prior biological knowledge. However, most of the information utilized by these methods is at the level of genes, limiting analyses to variants that are in or proximate to coding regions. We propose a new method that integrates protein protein interaction (PPI) as well as expression quantitative trait loci (eQTL) data to identify sets of functionally related loci that are collectively associated with a trait of interest. We call such sets of loci “population covering locus sets” (PoCos). The contributions of the proposed approach are three-fold: 1) We consider all possible genotype models for each locus, thereby enabling identification of combinatorial relationships between multiple loci. 2) We develop a framework for the integration of PPI and eQTL into a heterogenous network model, enabling efficient identification of functionally related variants that are associated with the disease. 3) We develop a novel method to integrate the genotypes of multiple loci in a PoCo into a representative genotype to be used in risk assessment. We test the proposed framework in the context of risk assessment for seven complex diseases, type 1 diabetes (T1D), type 2 diabetes (T2D), psoriasis (PS), bipolar disorder (BD), coronary artery disease (CAD), hypertension (HT), and multiple sclerosis (MS). Our results show that the proposed method significantly outperforms individual variant based risk assessment models as well as the state-of-the-art polygenic score. We also show that incorporation of eQTL data improves the performance of identified POCOs in risk assessment. We also assess the biological relevance of PoCos for three diseases that have similar biological mechanisms and

  1. Nutritional anemias.

    PubMed

    Hoffbrand, A V; Herbert, V

    1999-10-01

    Folate, vitamin B12, and iron are the subjects of active biochemical and molecular research so that further understanding of their metabolism in health and in a wide variety of Inherited and acquired diseases can be achieved. The roles of folate and vitamin B12 in cardiovascular and neurologic diseases and in neural tube defects (NTDs) will be further explored in the next decade. The effects of prophylactic therapy and of food fortification with the vitamins on these diseases remain to be established. Iron deficiency is a public health problem in all countries and prevention or treatment, particularly in children in developing countries, are major goals. The increased recent understanding of iron metabolism and absorption may clarify the etiology of diseases of iron metabolism and of dietary iron overload. Improved iron chelation therapy for transfusion-dependent patients with refractory anemias will continue to be actively researched over the next decades.

  2. Fine mapping of the chromosome 3p susceptibility locus in inflammatory bowel disease

    PubMed Central

    Hampe, J; Lynch, N; Daniels, S; Bridger, S; Macpherson, A; Stokkers, P; Forbes, A; Lennard-Jones, J; Mathew, C; Curran, M; Schreiber, S

    2001-01-01

    BACKGROUND AND AIMS—Genetic predisposition for inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic linkage studies. Genetic linkage of IBD to chromosome 3 has been observed previously. A high density analysis of chromosome 3p was performed to confirm prior linkages and elucidate potential genetic associations.
METHODS—Forty three microsatellite markers on chromosome 3 were genotyped in 353 affected sibling pairs of North European Caucasian extraction (average marker density 2 cM in the linkage interval). Marker order was defined by genetic and radiation hybrid techniques.
RESULTS—The maximum single point logarithm of odds (LOD) score was observed for Crohn's disease at D3S3591. Peak multipoint LOD scores of 1.65 and 1.40 for the IBD phenotype were observed near D3S1304 (distal 3p) and near D3S1283 in the linkage region previously reported. Crohn's disease contributed predominantly to the linkage. The transmission disequilibrium test showed significant evidence of association (p=0.009) between allele 4 of D3S1076 and the IBD phenotype (51 transmitted v 28 non-transmitted). Two known polymorphisms in the CCR2 and CCR5 genes were analysed, neither of which showed significant association with IBD. Additional haplotype associations were observed in the vicinity of D3S1076.
CONCLUSIONS—This study provides confirmatory linkage evidence for an IBD susceptibility locus on chromosome 3p and suggests that CCR2 and CCR5 are unlikely to be major susceptibility loci for IBD. The association findings in this region warrant further investigation.


Keywords: inflammatory bowel disease; fine mapping; chromosome 3 PMID:11156639

  3. Effects of chicken anemia virus and infectious bursal disease virus in commercial chickens.

    PubMed

    Toro, H; van Santen, V L; Hoerr, F J; Breedlove, C

    2009-03-01

    The effects of chicken anemia virus (CAV) and infectious bursal disease virus (IBDV) coinfection in commercial layer-type and meat-type (broiler) chickens with specific maternal immunity were evaluated. In addition, the broiler progeny used had been vaccinated in ovo against IBDV. Layer chickens were inoculated intramuscularly on day 3 of age with CAV and orally on day 7 of age with an IBDV standard strain (APHIS). Broiler chickens were exposed to CAV and/or an IBDV variant strain (AL2) via the drinking water on days 3 and 14 of age. Following CAV and IBDV inoculation neither mortality nor overt clinical disease was observed in any layer or broiler group. In spite of maternal immunity against both IBDV and CAV, mean hematocrits of all layer groups inoculated with CAV (CAV, CAV + APHIS) were lower than uninfected chickens. IBDV APHIS alone or in combination with CAV did not affect the layer weight gain. However, on day 30 of age and concomitantly with maternal antibody decay, bursa lymphocyte depletion became evident in CAV + APHIS-infected layer chickens. These birds (CAV + APHIS) also seroconverted to IBDV on day 35 of age. CAV persisted at low levels in the layer chickens throughout the experimental period in CAV- and CAV+APHIS-infected chickens. Similarly, infected broiler chickens did not show changes in weight gain. Compared to CAV-infected or uninfected controls, CAV+AL2- and AL2-infected broiler chickens showed significant lymphocyte depletion in the bursa as assessed both by bursal indices and histomorphometry. Broilers also seroconverted to IBDV after day 30 of age confirming that bursal lymphocyte depletion was due to IBDV resuming replication. Thymus histomorphometry revealed significant lymphocyte depletion in all infected broiler groups at 30 days of age, but only in CAV+AL2-infected broiler chickens at 41 days of age, suggesting that IBDV infection delayed repopulation of the thymus.

  4. Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease.

    PubMed Central

    Tutois, S; Montagutelli, X; Da Silva, V; Jouault, H; Rouyer-Fessard, P; Leroy-Viard, K; Guénet, J L; Nordmann, Y; Beuzard, Y; Deybach, J C

    1991-01-01

    A viable autosomal recessive mutation (named fch, or ferrochelatase deficiency) causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea. Homozygotes (fch/fch) display a hemolytic anemia, photosensitivity, cholestasis, and severe hepatic dysfunction. Protoporphyrin is found at high concentration in erythrocytes, serum, and liver. Ferrochelatase activity in various tissues is 2.7-6.3% of normal. Heterozygotes (+/fch) are not anemic and have normal liver function; they are not sensitive to light exposure; ferrochelatase activity is 45-65% of normal. Southern blot analysis using a ferrochelatase cDNA probe reveals no gross deletion of the ferrochelatase gene. This is the first spontaneous form of erythropoietic protoporphyria in the house mouse. Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form. Images PMID:1939658

  5. Prevalence and determinants of anemia in adults with complex congenital heart disease and ventricular dysfunction (subaortic right ventricle and single ventricle physiology).

    PubMed

    Collins, Nicholas; Piran, Sanaz; Harrison, Jeanine; Azevedo, Eduardo; Oechslin, Erwin; Silversides, Candice K

    2008-09-01

    Anemia is well recognized as a marker of poor prognosis in patients with acquired heart disease and heart failure. Adults with complex congenital heart disease and ventricular dysfunction (subaortic right ventricle or single-ventricle physiology) represent a different population, because they are typically much younger and have less co-morbidity compared with patients with acquired forms of heart disease. The purpose of this study was to evaluate the prevalence and determinants of anemia in this population. Baseline hemoglobin levels were recorded at the time of the initial clinic visit, and final hemoglobin levels were those recorded before death or transplantation or at study completion. Anemia was defined as hemoglobin <135 g/L in men and <120 g/L in women. One hundred sixty-seven patients (100 men, mean age 34 +/- 8 years, mean ejection fraction 35 +/- 9%) were included, 66 with atrial switch operations, 42 with congenitally corrected transposition of the great arteries, and 59 with Fontan physiology. The mean hemoglobin level at baseline was 149 +/- 22 g/L and at follow-up was 139 +/- 29 g/L. The overall prevalence of anemia was 29% at completion. Hyponatremia, decreased renal function, and the use of warfarin were independent predictors of anemia. In conclusion, anemia is common in patients with complex congenital heart disease and ventricular dysfunction, in particular those with Fontan physiology.

  6. Living with Aplastic Anemia

    MedlinePlus

    ... blood and bone marrow diseases, such as aplastic anemia. // Non Object? Updated: August 22, 2012 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA NO FEAR ACT OIG ...

  7. Quantitative trait locus analysis of fungal disease resistance factors on a molecular map of grapevine.

    PubMed

    Fischer, B M; Salakhutdinov, I; Akkurt, M; Eibach, R; Edwards, K J; Töpfer, R; Zyprian, E M

    2004-02-01

    A full-sibling F1 population comprising 153 individuals from the cross of 'Regent' x 'Lemberger' was employed to construct a genetic map based on 429 molecular markers. The newly-bred red grapevine variety 'Regent' has multiple field-resistance to fungal diseases inherited as polygenic traits, while 'Lemberger' is a traditional fungus-susceptible cultivar. The progeny segregate quantitatively for resistances to Plasmopara viticola and Uncinula necator, fungal pathogens that threaten viticulture in temperate areas. A double pseudo-testcross strategy was employed to construct the two parental maps under high statistical stringency for linkage to obtain a robust marker frame for subsequent quantitative trait locus (QTL) analysis. In total, 185 amplified fragment length polymorphism, 137 random amplified polymorphic DNA, 85 single sequence repeat and 22 sequence characterized amplified region or cleaved amplified polymorphic sequence markers were mapped. The maps were aligned by co-dominant or doubly heterozygous dominant anchor markers. Twelve pairs of homologous linkage groups could be integrated into consensus linkage groups. Resistance phenotypes and segregating characteristics were scored as quantitative traits in three or four growing seasons. Interval mapping reproducibly localized genetic factors that correlated with fungal disease resistances to specific regions on three linkage groups of the maternal 'Regent' map. A QTL for resistance to Uncinula necator was identified on linkage group 16, and QTLs for endurance to Plasmopara viticola on linkage groups 9 and 10 of 'Regent'. Additional QTLs for the onset of berry ripening ("veraison"), berry size and axillary shoot growth were identified. Berry color segregated as a simple trait in this cross of two red varieties and was mapped as a morphological marker. Six markers derived from functional genes could be localized. This dissection of polygenic fungus disease resistance in grapevine allows the development of

  8. Linkage mapping of the primary disease locus for collie eye anomaly.

    PubMed

    Lowe, Jennifer K; Kukekova, Anna V; Kirkness, Ewen F; Langlois, Mariela C; Aguirre, Gustavo D; Acland, Gregory M; Ostrander, Elaine A

    2003-07-01

    Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of the choroid and sclera segregating in several breeds of dog, including rough, smooth, and Border collies and Australian shepherds. The disease is reminiscent of the choroidal hypoplasia phenotype observed in humans in conjunction with craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can vary significantly; many dogs exhibit no obvious clinical consequences and retain apparently normal vision throughout life, while severely affected animals develop secondary retinal detachment, intraocular hemorrhage, and blindness. We report genetic studies establishing that the primary cea phenotype, choroidal hypoplasia, segregates as an autosomal recessive trait with nearly 100% penetrance. We further report linkage mapping of the primary cea locus to a 3.9-cM region of canine chromosome 37 (LOD = 22.17 at theta = 0.076), in a region corresponding to human chromosome 2q35. These results suggest the presence of a developmental regulatory gene important in ocular embryogenesis, with potential implications for other disorders of ocular vascularization.

  9. Lesions in the thymus and bone marrow in chicks with experimentally induced chicken infectious anemia disease

    PubMed Central

    Kuscu, Burak

    2008-01-01

    One-day-old SPF chicks were inoculated with the Cux-l strain of chicken infectious anemia virus (CIAV), and the clinical development of disease and its macroscopic and microscopic alterations in the thymus and bone marrow, were observed. Tissue sections of thymus and bone marrow were stained using the streptavidin-biotin peroxidase method and examined under light microscope for evaluation of antigenic intensities in tissues. Those findings were then compared with blood parameters and ELISA results obtained through collected sera during sacrifice procedures. We sought to determine: the localization of viral antigens in thymus and bone marrow tissues after inoculation, the correlation between antigen intensities and hematologic, serologic and histopathologic findings, definitive diagnostic criteria using histopathologic and immunoperoxidase methods, and the reliability of these methods in the diagnosis of CIAV infection. For this purpose, 83, one-day-old SPF chicks were used. The birds were divided into experimental (n = 52) and control (n = 26) groups. A virus dose of TCID50 of 100,000/ml was administered intramuscularly to every bird in the experimental group. Based on the results of this study, we have suggested that clinical examination, along with macroscopic and microscopic evaluation of the thymus and bone marrow, maybe undertaken starting from day 7 post-inoculation (PI). ELISA, might be of value, as it might give consistent results starting from day 14 PI. However, the most reliable results were obtained through examination of thymus and bone marrow sections from infected birds stained by immunoperoxidase technique, as early as day 4 PI. PMID:18296884

  10. Meta-analysis of Parkinson disease: Identification of a novel locus, RIT2

    PubMed Central

    Pankratz, Nathan; Beecham, Gary W.; DeStefano, Anita L.; Dawson, Ted M.; Doheny, Kimberly F.; Factor, Stewart A.; Hamza, Taye H.; Hung, Albert Y.; Hyman, Bradley T.; Ivinson, Adrian J.; Krainc, Dmitri; Latourelle, Jeanne C.; Clark, Lorraine N.; Marder, Karen; Martin, Eden R.; Mayeux, Richard; Ross, Owen A.; Scherzer, Clemens R.; Simon, David K.; Tanner, Caroline; Vance, Jeffery M.; Wszolek, Zbigniew K.; Zabetian, Cyrus P.; Myers, Richard H.; Payami, Haydeh; Scott, William K.; Foroud, Tatiana

    2011-01-01

    Objective Genome-wide association (GWAS) methods have identified genes contributing to Parkinson disease (PD); we sought to identify additional genes associated with PD susceptibility. Methods A two stage design was used. First, individual level genotypic data from five recent PD GWAS (Discovery Sample: 4,238 PD cases and 4,239 controls) were combined. Following imputation, a logistic regression model was employed in each dataset to test for association with PD susceptibility and results from each dataset were meta-analyzed. Second, 768 SNPs were genotyped in an independent Replication Sample (3,738 cases and 2,111 controls). Results Genome-wide significance was reached for SNPs in SNCA (rs356165, G: odds ratio (OR)=1.37; p=9.3 × 10−21), MAPT (rs242559, C: OR=0.78; p=1.5 × 10−10), GAK/DGKQ (rs11248051, T:OR=1.35; p=8.2 × 10−9/ rs11248060, T: OR=1.35; p=2.0×10−9), and the HLA region (rs3129882, A: OR=0.83; p=1.2 × 10−8), which were previously reported. The Replication Sample confirmed the associations with SNCA, MAPT, and the HLA region and also with GBA (E326K OR=1.71; p=5 × 10−8 Combined Sample) (N370 OR=3.08; p=7 × 10−5 Replication sample). A novel PD susceptibility locus, RIT2, on chromosome 18 (rs12456492; p=5 × 10−5 Discovery Sample; p=1.52 × 10−7 Replication sample; p=2 × 10−10 Combined Sample) was replicated. Conditional analyses within each of the replicated regions identified distinct SNP associations within GBA and SNCA, suggesting that there may be multiple risk alleles within these genes. Interpretation We identified a novel PD susceptibility locus, RIT2, replicated several previously identified loci, and identified more than one risk allele within SNCA and GBA. PMID:22451204

  11. Treatment of anemia in heart failure: potential risks and benefits of intravenous iron therapy in cardiovascular disease.

    PubMed

    Jelani, Qurat-ul-ain; Katz, Stuart D

    2010-01-01

    Iron-deficiency anemia is common in patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a subgroup analysis also suggest that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients.

  12. Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'.

    PubMed

    De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim

    2017-04-01

    'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

  13. Pentoxifylline for Anemia in Chronic Kidney Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Bolignano, Davide; D’Arrigo, Graziella; Pisano, Anna; Coppolino, Giuseppe

    2015-01-01

    Background Pentoxifylline (PTX) is a promising therapeutic approach for reducing inflammation and improving anemia associated to various systemic disorders. However, whether this agent may be helpful for anemia management also in CKD patients is still object of debate. Study Design Systematic review and meta-analysis. Population Adults with CKD (any KDOQI stage, including ESKD patients on regular dialysis) and anemia (Hb<13 g/dL in men or < 12 g/dL in women). Search Strategy and Sources Cochrane CENTRAL, EMBASE, Ovid-MEDLINE and PubMed were searched for studies providing data on the effects of PTX on anemia parameters in CKD patients without design or follow-up restriction. Intervention PTX derivatives at any dose regimen. Outcomes Hemoglobin, hematocrit, ESAs dosage and resistance (ERI), iron indexes (ferritin, serum iron, TIBC, transferrin and serum hepcidin) and adverse events. Results We retrieved 11 studies (377 patients) including seven randomized controlled trials (all comparing PTX to placebo or standard therapy) one retrospective case-control study and three prospective uncontrolled studies. Overall, PTX increased hemoglobin in three uncontrolled studies but such improvement was not confirmed in a meta-analysis of seven studies (299 patients) (MD 0.12 g/dL, 95% CI -0.22 to 0.47). Similarly, there were no conclusive effects of PTX on hematocrit, ESAs dose, ferritin and TSAT in pooled analyses. Data on serum iron, ERI, TIBC and hepcidin were based on single studies. No evidence of increased rate of adverse events was also noticed. Limitations Small sample size and limited number of studies. High heterogeneity among studies with respect to CKD and anemia severity, duration of intervention and responsiveness/current therapy with iron or ESAs. Conclusions There is currently no conclusive evidence supporting the utility of pentoxifylline for improving anemia control in CKD patients. Future trials designed on hard, patient-centered outcomes with larger sample

  14. Pernicious anemia

    MedlinePlus

    ... physical exam. Tests that may be done include: Bone marrow examination (only needed if diagnosis is unclear) ... Alternative Names Macrocytic achylic anemia; Congenital pernicious anemia; Juvenile ... Review Date 2/1/2016 ...

  15. Aplastic Anemia

    MedlinePlus

    Aplastic anemia is a rare but serious blood disorder. If you have it, your bone marrow doesn't make ... blood cells. There are different types, including Fanconi anemia. Causes include Toxic substances, such as pesticides, arsenic, ...

  16. Unraveling Genomic Complexity at a Quantitative Disease Resistance Locus in Maize

    PubMed Central

    Jamann, Tiffany M.; Poland, Jesse A.; Kolkman, Judith M.; Smith, Laurie G.; Nelson, Rebecca J.

    2014-01-01

    Multiple disease resistance has important implications for plant fitness, given the selection pressure that many pathogens exert directly on natural plant populations and indirectly via crop improvement programs. Evidence of a locus conditioning resistance to multiple pathogens was found in bin 1.06 of the maize genome with the allele from inbred line “Tx303” conditioning quantitative resistance to northern leaf blight (NLB) and qualitative resistance to Stewart’s wilt. To dissect the genetic basis of resistance in this region and to refine candidate gene hypotheses, we mapped resistance to the two diseases. Both resistance phenotypes were localized to overlapping regions, with the Stewart’s wilt interval refined to a 95.9-kb segment containing three genes and the NLB interval to a 3.60-Mb segment containing 117 genes. Regions of the introgression showed little to no recombination, suggesting structural differences between the inbred lines Tx303 and “B73,” the parents of the fine-mapping population. We examined copy number variation across the region using next-generation sequencing data, and found large variation in read depth in Tx303 across the region relative to the reference genome of B73. In the fine-mapping region, association mapping for NLB implicated candidate genes, including a putative zinc finger and pan1. We tested mutant alleles and found that pan1 is a susceptibility gene for NLB and Stewart’s wilt. Our data strongly suggest that structural variation plays an important role in resistance conditioned by this region, and pan1, a gene conditioning susceptibility for NLB, may underlie the QTL. PMID:25009146

  17. Construction of a yeast artificial chromosome contig encompassing the chromosome 14 Alzheimer`s disease locus

    SciTech Connect

    Sharma, V.; Bonnycastle, L.; Poorkai, P.

    1994-09-01

    We have constructed a yeast artificial chromosome (YAC) contig of chromosome 14q24.3 which encompasses the chromosome 14 Alzheimer`s disease locus (AD3). Determined by linkage analysis of early-onset Alzheimer`s disease kindreds, this interval is bounded by the genetic markers D14S61-D14S63 and spans approximately 15 centimorgans. The contig consists of 29 markers and 74 YACs of which 57 are defined by one or more sequence tagged sites (STSs). The STS markers comprise 5 genes, 16 short tandem repeat polymorphisms and 8 cDNA clones. An additional number of genes, expressed sequence tags and cDNA fragments have been identified and localized to the contig by hybridization and sequence analysis of anonymous clones isolated by cDNA direct selection techniques. A minimal contig of about 15 YACs averaging 0.5-1.5 megabase in length will span this interval and is, at first approximation, in rough agreement with the genetic map. For two regions of the contig, our coverage has relied on L1/THE fingerprint and Alu-PCR hybridization data of YACs provided by CEPH/Genethon. We are currently developing sequence tagged sites from these to confirm the overlaps revealed by the fingerprint data. Among the genes which map to the contig are transforming growth factor beta 3, c-fos, and heat shock protein 2A (HSPA2). C-fos is not a candidate gene for AD3 based on the sequence analysis of affected and unaffected individuals. HSPA2 maps to the proximal edge of the contig and Calmodulin 1, a candidate gene from 4q24.3, maps outside of the region. The YAC contig is a framework physical map from which cosmid or P1 clone contigs can be constructed. As more genes and cDNAs are mapped, a highly resolved transcription map will emerge, a necessary step towards positionally cloning the AD3 gene.

  18. CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation

    PubMed Central

    Reznichenko, Anna; Snieder, Harold; van den Born, Jacob; de Borst, Martin H.; Damman, Jeffrey; van Dijk, Marcory C. R. F.; van Goor, Harry; Hepkema, Bouke G.; Hillebrands, Jan-Luuk; Leuvenink, Henri G. D.; Niesing, Jan; Bakker, Stephan J. L.; Seelen, Marc; Navis, Gerjan

    2012-01-01

    Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8–9.2] years (longitudinal study) documenting ESRD in transplanted kidneys – graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys. PMID:22574174

  19. Identification of a locus controlling Verticillium disease symptom response in Arabidopsis thaliana.

    PubMed

    Veronese, Paola; Narasimhan, Meena L; Stevenson, Rebecca A; Zhu, Jian-K; Weller, Stephen C; Subbarao, Krishna V; Bressan, Ray A

    2003-09-01

    Verticillium dahliae Klebahn is a soil-borne fungal pathogen causing vascular diseases. The pathogen penetrates the host through the roots, spreads through the xylem, and systemically colonizes both resistant and susceptible genotypes. To elucidate the genetic and molecular bases of plant-Verticillium interactions, we have developed a pathosystem utilizing Arabidopsis thaliana and an isolate of V. dahliae pathogenic to both cruciferous and non-cruciferous crops. Relative tolerance (based on symptom severity) but no immunity was found in a survey of Arabidopsis ecotypes. Anthocyanin accumulation, stunting, and chlorosis were common symptoms. Specific responses of the more susceptible ecotype Columbia were induction of early flowering and dying. The more tolerant ecotype C-24 was characterized by pathogen-induced delay of transition to flowering and mild chlorosis symptoms. Genetic analysis indicated that a single dominant locus, Verticillium dahliae-tolerance (VET1), likely functioning also as a negative regulator of the transition to flowering, was able to convey increased tolerance. VET1 was mapped on chromosome IV. The differential symptom responses observed between ecotypes were not correlated with different rates of fungal tissue colonization or with differential transcript accumulation of PR-1 and PDF1.2 defense genes whose activation was not detected during the Arabidopsis-V. dahliae interaction. Impairment in salicylic acid (SA)- or jasmonic acid (JA)-dependent signaling did not cause hypersensitivity to the fungal infection, whereas ethylene insensitivity led to reduced chlorosis and ABA deficiency to reduced anthocyanin accumulation. The results of this study clearly indicated that the ability of V. dahliae to induce disease symptoms is also connected to the genetic control of development and life span in Arabidopsis.

  20. Unraveling genomic complexity at a quantitative disease resistance locus in maize.

    PubMed

    Jamann, Tiffany M; Poland, Jesse A; Kolkman, Judith M; Smith, Laurie G; Nelson, Rebecca J

    2014-09-01

    Multiple disease resistance has important implications for plant fitness, given the selection pressure that many pathogens exert directly on natural plant populations and indirectly via crop improvement programs. Evidence of a locus conditioning resistance to multiple pathogens was found in bin 1.06 of the maize genome with the allele from inbred line "Tx303" conditioning quantitative resistance to northern leaf blight (NLB) and qualitative resistance to Stewart's wilt. To dissect the genetic basis of resistance in this region and to refine candidate gene hypotheses, we mapped resistance to the two diseases. Both resistance phenotypes were localized to overlapping regions, with the Stewart's wilt interval refined to a 95.9-kb segment containing three genes and the NLB interval to a 3.60-Mb segment containing 117 genes. Regions of the introgression showed little to no recombination, suggesting structural differences between the inbred lines Tx303 and "B73," the parents of the fine-mapping population. We examined copy number variation across the region using next-generation sequencing data, and found large variation in read depth in Tx303 across the region relative to the reference genome of B73. In the fine-mapping region, association mapping for NLB implicated candidate genes, including a putative zinc finger and pan1. We tested mutant alleles and found that pan1 is a susceptibility gene for NLB and Stewart's wilt. Our data strongly suggest that structural variation plays an important role in resistance conditioned by this region, and pan1, a gene conditioning susceptibility for NLB, may underlie the QTL.

  1. Nutritional anemias and the elderly.

    PubMed

    Carmel, Ralph

    2008-10-01

    Nutritional anemias are important because they are easily reversed and because their underlying causes, most often unrelated to dietary intake, require individualized assessment. Iron-deficiency anemia (IDA) usually results from iron losses accompanying chronic bleeding, including loss to intestinal parasites, or from gastric disorders or malabsorption in the elderly. Cobalamin-deficiency anemia, the only nutritional anemia with predilection for the elderly, nearly always stems from failure of intrinsic factor (IF)-related absorption. Folate-deficiency anemia, the only nutritional anemia usually caused by poor intake, has nearly disappeared in countries that fortify food with folic acid. Copper-deficiency anemia, which usually results from malabsorptive disorders or from medical or nutritional interventions that provide inadequate copper or excess zinc, is uncommon but increasingly recognized. The prevalences of nutritional anemias, which are not always distinguished from non-anemic deficiency, are uncertain. The mean corpuscular volume (MCV) provides an essential diagnostic tool leading to judicious matching of relevant biochemical changes with relevant anemia. Nutritional anemias usually feature abnormal MCV, whereas the predominant anemias in the aged, especially the anemias of chronic disease/chronic inflammation (ACD/ACI), of renal failure, and of unknown causes, are typically normocytic.

  2. Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease.

    PubMed

    Fisher, Sheila A; Tremelling, Mark; Anderson, Carl A; Gwilliam, Rhian; Bumpstead, Suzannah; Prescott, Natalie J; Nimmo, Elaine R; Massey, Dunecan; Berzuini, Carlo; Johnson, Christopher; Barrett, Jeffrey C; Cummings, Fraser R; Drummond, Hazel; Lees, Charlie W; Onnie, Clive M; Hanson, Catherine E; Blaszczyk, Katarzyna; Inouye, Mike; Ewels, Philip; Ravindrarajah, Radhi; Keniry, Andrew; Hunt, Sarah; Carter, Martyn; Watkins, Nick; Ouwehand, Willem; Lewis, Cathryn M; Cardon, Lon; Lobo, Alan; Forbes, Alastair; Sanderson, Jeremy; Jewell, Derek P; Mansfield, John C; Deloukas, Panos; Mathew, Christopher G; Parkes, Miles; Satsangi, Jack

    2008-06-01

    We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.

  3. Genome scan in familial late-onset Alzheimer's disease: a locus on chromosome 6 contributes to age-at-onset.

    PubMed

    Zhao, Wei; Marchani, Elizabeth E; Cheung, Charles Y K; Steinbart, Ellen J; Schellenberg, Gerard D; Bird, Thomas D; Wijsman, Ellen M

    2013-03-01

    Alzheimer's disease (AD) is a common, genetically complex, fatal neurodegenerative disorder of late life. Although several genes are known to play a role in early-onset AD, identification of the genetic basis of late onset AD (LOAD) has been challenging, with only the APOE gene known to have a high contribution to both AD risk and age-at-onset. Here, we present the first genome-scan analysis of the complete, well-characterized University of Washington LOAD sample of 119 pedigrees, using age-at-onset as the trait of interest. The analysis approach used allows for a multilocus trait model while at the same time accommodating age censoring, effects of APOE as a known genetic covariate, and full pedigree and marker information. The results provide strong evidence for linkage of loci contributing to age-at-onset to genomic regions on chromosome 6q16.3, and to 19q13.42 in the region of the APOE locus. There was evidence for interaction between APOE and the locus on chromosome 6q and suggestive evidence for linkage to chromosomes 11p13, 15q12-14, and 19p13.12. These results provide the first independent confirmation of an AD age-at-onset locus on chromosome 6 and suggest that further efforts towards identifying the underlying causal locus or loci are warranted.

  4. Feline porphyria associated with anemia, severe hepatic disease, and renal calculi

    PubMed Central

    Schnier, Jonathan J.; Hanna, Paul

    2010-01-01

    A 13-year-old, neutered male domestic cat presented with signs of weight loss, anemia, and hepatomegaly. Pathognomonic signs of porphyria were identified. Charcoal-like renal calculi and severe liver changes were observed, neither of which has been previously reported in association with feline porphyria. PMID:21197209

  5. Feline porphyria associated with anemia, severe hepatic disease, and renal calculi.

    PubMed

    Schnier, Jonathan J; Hanna, Paul

    2010-10-01

    A 13-year-old, neutered male domestic cat presented with signs of weight loss, anemia, and hepatomegaly. Pathognomonic signs of porphyria were identified. Charcoal-like renal calculi and severe liver changes were observed, neither of which has been previously reported in association with feline porphyria.

  6. Severity of Anemia Predicts Hospital Length of Stay but Not Readmission in Patients with Chronic Kidney Disease: A Retrospective Cohort Study.

    PubMed

    Garlo, Katherine; Williams, Deanna; Lucas, Lee; Wong, Rocket; Botler, Joel; Abramson, Stuart; Parker, Mark G

    2015-06-01

    The aim of this study was to examine the relationship of severe anemia to hospital readmission and length of stay (LOS) in patients with chronic kidney disease (CKD) stage 3-5. Compared with the general population, patients with moderate CKD have a higher hospital readmission rate and LOS. Anemia in patients with moderate CKD is associated with higher morbidity and mortality. The influence of anemia on hospital outcomes in patients with moderate CKD has not been characterized.We conducted a retrospective cohort study at Maine Medical Center, a 606-bed academic tertiary care hospital. Patients with CKD stages 3-5 and not on dialysis admitted during February 2013 to January 2014 were eligible. Patients with end stage renal disease on hemodialysis or peritoneal dialysis, kidney transplant, acute kidney injury, gastrointestinal bleeding, active malignancy, pregnancy, and surgery were excluded. The cohort was split into severe anemia (hemoglobin ≤9  g/dL) versus a comparison group (hemoglobin >9 g /dL), and examined for differences in 30-day hospital readmission and LOS.In this study, the data of 1141 patients were included, out of which 156 (13.7%) had severe anemia (mean hemoglobin 8.1 g/dL, SD 0.8). Severe anemia was associated with increased hospital LOS (mean 6.4 (SD 6.0) days vs mean 4.5 (SD 4.0) days, P < 0.001). The difference was 1.7 day longer (95% CI 0.94, 2.45). There was no difference in readmission rate (mean 11.5% vs 10.2%, P = 0.7).Patients with moderate CKD and severe anemia are at risk for increased hospital LOS. Interventions targeting this high-risk population, including outpatient management of anemia, may benefit patient care and save costs through improved hospital outcomes.

  7. Heavy metals in locus ceruleus and motor neurons in motor neuron disease

    PubMed Central

    2013-01-01

    Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485

  8. Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer`s disease but is not causative

    SciTech Connect

    Bennett, C.; Crawford, F.; Osborne, A.; Diaz, P.

    1995-02-27

    An association has been observed in several independent data sets between late onset Alzheimer`s Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the {epsilon}4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non-stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD. 19 refs., 1 fig., 2 tabs.

  9. Study of anemia in nondialysis dependent chronic kidney disease with special reference to serum hepcidin

    PubMed Central

    Goyal, H.; Mohanty, S.; Sharma, M.; Rani, A.

    2017-01-01

    We studied the role of serum hepcidin in anemia of chronic kidney disease (CKD) in a hospital-based cross-sectional study. Serum hepcidin, ferritin, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated in patients of CKD. Hepcidin levels were increased in patients as compared to healthy adults. Hepcidin levels increased as CKD progressed through stage 3–5 (P trend = 0.015) but did not correlate with estimated glomerular filtration rate. Hepcidin correlated positively with ferritin (P < 0.0001) and transferrin saturation (TSAT) (P = 0.0217) and negatively with erythropoietin (EPO) levels (P = 0.0258) but did not correlate with either hsCRP or estimated glomerular filtration rate. Iron status influenced hepcidin levels of patients. Patients were divided according to iron status on the basis of TSAT and serum ferritin levels. We observed that while absolute iron deficiency (transferrin saturation <20%, ferritin <40 ng/ml) is associated with downregulation of hepcidin, hepcidin is elevated in other two categories of CKD patients (P = 0.0039). Iron status of patients also influenced interaction between hepcidin and hemoglobin (Hb). Hepcidin correlated negatively with Hb in patients with sufficient iron status (r = −0.7452, P < 0.0001) but nearly correlated positively with Hb in patients with absolute iron deficiency (r = 0.9428, P = 0.0572). Almost similar association persisted when cutoff value for serum ferritin was raised to 100 ng/ml as per NKF/KDOQI 2006 clinical practice guidelines except that no association was observed in absolute iron deficiency category. Cutoff value for hepcidin for differentiating absolute iron deficiency from other categories in our study population is ≤ 34 ng/ml (area under curve = 0.836, P < 0.0001). In conclusion, serum hepcidin level is increased in nondialysis CKD patients as compared to healthy adults possibly due to associated inflammation and decreased renal clearance. Furthermore, iron status modifies

  10. Hepcidin as a predictive factor and therapeutic target in erythropoiesis-stimulating agent treatment for anemia of chronic disease in rats.

    PubMed

    Theurl, Milan; Nairz, Manfred; Schroll, Andrea; Sonnweber, Thomas; Asshoff, Malte; Haschka, David; Seifert, Markus; Willenbacher, Wolfgang; Wilflingseder, Doris; Posch, Wilfried; Murphy, Anthony T; Witcher, Derrick R; Theurl, Igor; Weiss, Günter

    2014-09-01

    Anemia of chronic disease is a multifactorial disorder, resulting mainly from inflammation-driven reticuloendothelial iron retention, impaired erythropoiesis, and reduced biological activity of erythropoietin. Erythropoiesis-stimulating agents have been used for the treatment of anemia of chronic disease, although with varying response rates and potential adverse effects. Serum concentrations of hepcidin, a key regulator of iron homeostasis, are increased in patients with anemia of chronic disease and linked to the pathogenesis of this disease, because hepcidin blocks cellular iron egress, thus limiting availability of iron for erythropoiesis. We tested whether serum hepcidin levels can predict and affect the therapeutic efficacy of erythropoiesis-stimulating agent treatment using a well-established rat model of anemia of chronic disease. We found that high pre-treatment hepcidin levels correlated with an impaired hematologic response to an erythropoiesis-stimulating agent in rats with anemia of chronic disease. Combined treatment with an erythropoiesis-stimulating agent and an inhibitor of hepcidin expression, LDN-193189, significantly reduced serum hepcidin levels, mobilized iron from tissue stores, increased serum iron levels and improved hemoglobin levels more effectively than did the erythropoiesis-stimulating agent or LDN-193189 monotherapy. In parallel, both the erythropoiesis-stimulating agent and erythropoiesis-stimulating agent/LDN-193189 combined reduced the expression of cytokines known to inhibit erythropoiesis. We conclude that serum hepcidin levels can predict the hematologic responsiveness to erythropoiesis-stimulating agent therapy in anemia of chronic disease. Pharmacological inhibition of hepcidin formation improves the erythropoiesis-stimulating agent's therapeutic efficacy, which may favor a reduction of erythropoiesis-stimulating agent dosages, costs and side effects.

  11. A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease.

    PubMed

    Fujiwara, Tohru; Ikeda, Takashi; Nagasaka, Yuki; Okitsu, Yoko; Katsuoka, Yuna; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Ichinohasama, Ryo; Tomosugi, Naohisa; Harigae, Hideo

    2013-01-01

    Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. The expression of the hepcidin gene, HAMP, is increased in patients with anemia of chronic disease. Previously, the synthetic compound K7174 was identified through chemical screening as a novel inhibitor of the adhesion of monocytes to cytokine-stimulated endothelial cells. K7174 also ameliorated anemia induced by inflammatory cytokines in mice, which suggests a possible involvement of hepcidin regulation. The present study was performed to assess the impact of K7174 on hepcidin expression in a human hematoma cell line and in mice in vivo. We first demonstrated that K7174 treatment in HepG2 cells significantly decreased HAMP expression. Then, we conducted microarray analysis to determine the molecular mechanism by which K7174 inhibits HAMP expression. Transcriptional profiling confirmed the downregulation of HAMP. Surprisingly, we found that K7174 strongly induced GDF15, known as a negative regulator of HAMP expression. Western blotting analysis as well as ELISA confirmed the induction of GDF15 by K7174 treatment. Furthermore, K7174-mediated HAMP suppression was rescued by the silencing of GDF15 expression. Interestingly, we found that K7174 also upregulates CEBPB. Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB could contribute to K7174-mediated transcriptional activation of GDF15. Subsequently, we also examined whether K7174 inhibits hepcidin expression in mice. Quantitative RT-PCR analysis with liver samples from K7174-treated mice demonstrated significant upregulation of Gdf15 and downregulation of Hamp expression, as compared to control mice. Furthermore, serum hepcidin concentration was also significantly decreased in K7174-treated mice. In conclusion, K7174 inhibits hepcidin expression partly by inducing GDF15. K-7174 may be a potential therapeutic option to treat anemia of chronic

  12. Characterization of a disease susceptibility locus for exploring an efficient way to improve rice resistance against bacterial blight.

    PubMed

    Cheng, Qi; Mao, Weihua; Xie, Wenya; Liu, Qinsong; Cao, Jianbo; Yuan, Meng; Zhang, Qinglu; Li, Xianghua; Wang, Shiping

    2017-03-01

    Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is the most harmful bacterial disease of rice worldwide. Previously, we characterized major disease resistance (MR) gene xa25, which confers race-specific resistance to Xoo strain PXO339. The xa25 is a recessive allele of the SWEET13 locus, but SWEET13's interaction with PXO339 and how efficiently using this locus for rice breeding still need to be defined. Here we show that the SWEET13 allele from rice Zhenshan 97 is a susceptibility gene to PXO339. Using this allele's promoter to regulate xa25 resulted in disease, suggesting that the promoter is a key determinant in SWEET13 caused disease in Zhanshan 97 after PXO339 infection. PXO339 transcriptionally induces SWEET13 to cause disease. Partial suppressing SWEET13 expression leads to a high level of resistance to PXO339. Thus, the transcriptionally suppressed SWEET13 functions as xa25 in resistance to PXO339. Hybrid rice is widely grown in many countries. However, recessive MR genes have not been efficiently used for disease resistance breeding in hybrid rice production for both parents of the hybrid have to carry the same recessive gene. However, the suppressed SWEET13 functions dominantly, which will have advantage to improve the resistance of hybrid rice to xa25-incomptible Xoo.

  13. Linkage Analysis in Autoimmune Addison’s Disease: NFATC1 as a Potential Novel Susceptibility Locus

    PubMed Central

    Mitchell, Anna L.; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U.; Vaidya, Bijay; Erichsen, Martina M.; Darlay, Rebecca; Husebye, Eystein S.; Cordell, Heather J.; Pearce, Simon H. S.

    2015-01-01

    Background Autoimmune Addison’s disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. Methods DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. Results In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. Conclusion This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis. PMID:26042420

  14. Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease.

    PubMed

    Bueno, Clara; Roldan, Mar; Anguita, Eduardo; Romero-Moya, Damia; Martín-Antonio, Beatriz; Rosu-Myles, Michael; del Cañizo, Consuelo; Campos, Francisco; García, Regina; Gómez-Casares, Maite; Fuster, Jose Luis; Jurado, Manuel; Delgado, Mario; Menendez, Pablo

    2014-07-01

    Aplastic anemia is a life-threatening bone marrow failure disorder characterized by peripheral pancytopenia and marrow hypoplasia. The majority of cases of aplastic anemia remain idiopathic, although hematopoietic stem cell deficiency and impaired immune responses are hallmarks underlying the bone marrow failure in this condition. Mesenchymal stem/stromal cells constitute an essential component of the bone marrow hematopoietic microenvironment because of their immunomodulatory properties and their ability to support hematopoiesis, and they have been involved in the pathogenesis of several hematologic malignancies. We investigated whether bone marrow mesenchymal stem cells contribute, directly or indirectly, to the pathogenesis of aplastic anemia. We found that mesenchymal stem cell cultures can be established from the bone marrow of aplastic anemia patients and display the same phenotype and differentiation potential as their counterparts from normal bone marrow. Mesenchymal stem cells from aplastic anemia patients support the in vitro homeostasis and the in vivo repopulating function of CD34(+) cells, and maintain their immunosuppressive and anti-inflammatory properties. These data demonstrate that bone marrow mesenchymal stem cells from patients with aplastic anemia do not have impaired functional and immunological properties, suggesting that they do not contribute to the pathogenesis of the disease.

  15. Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus

    PubMed Central

    Labbé, Catherine; Ogaki, Kotaro; Lorenzo-Betancor, Oswaldo; Carrasquillo, Minerva M.; Heckman, Michael G.; McCarthy, Allan; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Dickson, Dennis W.; Uitti, Ryan J.; Wszolek, Zbigniew K.; Ross, Owen A.

    2015-01-01

    Genome-wide association studies (GWAS) in Parkinson’s disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11–1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD. PMID:26090850

  16. Thalassemia and sickle cell anemia in Swedish immigrants: Genetic diseases have become global

    PubMed Central

    Hemminki, Kari; Li, Xinjun; Försti, Asta; Sundquist, Jan; Sundquist, Kristina

    2015-01-01

    Aims: Some 15% of the Swedish population is born outside Sweden, originating from all continents of the world. Thalassemia and sickle cell anemia constitute the most common inherited recessive disorders globally and they are endemic in areas of Africa and Asia, origins of many immigrants to Sweden. We aimed at investigating the origins of the Swedish sickle cell and thalassemia patients. Methods: Patients were identified using data from the Swedish Hospital Discharge Register since 1987 and from the Outpatient Register since 2001 up to year 2010. Results: A total of 3064 persons were diagnosed with thalassemia. The incidence was highest, 62.9/100,000 for immigrants from Thailand, followed by Iraqis (47.1/100,000); the rate was 0.7/100,000 among those born in Sweden. The total number of sickle cell anemia patients was 584 and the highest rate of 13.0/100,000 was found for Sub-Saharan immigrants. For thalassemia, 363 of the patients were siblings, while for sickle cell anemia, 180 were siblings. Conclusions: The data showed that >90% of sickle cell and thalassemia patients were first- or second-generation immigrants to Sweden and the endemic regions for these were the origins of immigrants with the highest incidence. Global immigration provides global challenges to national health care systems. PMID:27092253

  17. Two-locus models of disease: Comparison of likelihood and nonparametric linkage methods

    SciTech Connect

    Goldin, L.R. ); Weeks, D.E. )

    1993-10-01

    The power to detect linkage for likelihood and nonparametric (Haseman-Elston, affected-sib-pair, and affected-pedigree-member) methods is compared for the case of a common, dichotomous trait resulting from the segregation of two loci. Pedigree data for several two-locus epistatic and heterogeneity models have been simulated, with one of the loci linked to a marker locus. Replicate samples of 20 three-generation pedigrees (16 individuals/pedigree) were simulated and then ascertained for having at least 6 affected individuals. The power of linkage detection calculated under the correct two-locus model is only slightly higher than that under a single locus model with reduced penetrance. As expected, the nonparametric linkage methods have somewhat lower power than does the lod-score method, the difference depending on the mode of transmission of the linked locus. Thus, for many pedigree linkage studies, the lod-score method will have the best power. However, this conclusion depends on how many times the lod score will be calculated for a given marker. The Haseman-Elston method would likely be preferable to calculating lod scores under a large number of genetic models (i.e., varying both the mode of transmission and the penetrances), since such an analysis requires an increase in the critical value of the lod criterion. The power of the affected-pedigree-member method is lower than the other methods, which can be shown to be largely due to the fact that marker genotypes for unaffected individuals are not used. 31 refs., 1 fig., 5 tabs.

  18. Prevalence of anemia and its impact on mortality in patients with acute exacerbation of chronic obstructive pulmonary disease in a developing country setting.

    PubMed

    Rahimi-Rad, Mohammad Hossein; Sadighi, Tannaz; Rabieepour, Masomeh; Dinparast, Reza; RahimiRad, Shagayegh

    2015-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is going to be the third most common cause of death worldwide. The natural course of COPD is interrupted by acute exacerbations (AECOPD) with an overall mortality rate of 10%. Anemia is a well-known independent predictor of mortality in several chronic diseases. Little is known about the impact of anemia on mortality in AECOPD. The aims of this study were to determine the prevalence of anemia in AECOPD patients and its impact on mortality in a developing country setting. We retrospectively studied 200 hospitalized patients with AECOPD (100 died in hospital and 100 survived) in Imam Khomeini teaching hospital, Urmia, Iran. Prevalence of anemia between deceased and surviving patients compared by using x-square test. Mean admission day Hb and Hct level were compared between the two groups by using Student t-test. Anemia was defined according to WHO criteria: Hb<13 g/dl in males; Hb<12 g/dl in females. The prevalence of anemia was significantly higher in patients who died in hospital compared to those who survived (72% vs. 49%, p=0.001 and OR=2.68). The mean ±SD Hb level was 11.5±2.7 g/dl among deceased patients vs. 13.0±2.0 g/dl among survivors (p value<0.001). The duration of hospitalization was significantly higher (p<0,001) in anemic patients (mean 13.28 days in anemic vs. 7.0 days in non-anemic patients). In bivariate correlation analysis, Hb was positively correlated with FEV1 (r=+0.210, p=0.011) and negatively with duration of hospitalization (r=-0.389, p=0.000). Anemia was common in AECOPD patients in this developing country setting and was significantly associated with in hospital mortality.

  19. Pregnancy Complications: Anemia

    MedlinePlus

    ... Close X Home > Complications & Loss > Pregnancy complications > Anemia Anemia E-mail to a friend Please fill in ... anemia at a prenatal care visit . What causes anemia? Usually, a woman becomes anemic (has anemia) because ...

  20. Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy.

    PubMed

    Jiang, Yao; Zhang, Jingjing; Yuan, Yanggang; Zha, Xiaoming; Xing, Changying; Shen, Chong; Shen, Zhixiang; Qin, Chao; Zeng, Ming; Yang, Guang; Mao, Huijuan; Zhang, Bo; Yu, Xiangbao; Sun, Bin; Ouyang, Chun; Xu, Xueqiang; Ge, Yifei; Wang, Jing; Zhang, Lina; Cheng, Chen; Yin, Caixia; Zhang, Jing; Chen, Huimin; Ma, Haoyang; Wang, Ningning

    2016-06-16

    Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m(2). Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD.

  1. Clinical utility of Beckman-Coulter Gen's reticulocyte analysis in the study of anemia of chronic disease (ACD).

    PubMed

    Rodrigues, Ana; Ortega, Carlos; Santos, Luís; Teixeira, Alexandre; Dinis, Maria Joáo; Vasconcelos, Iponina; Lacerda, Jorge; Fonseca, Elisa

    2007-01-01

    The aim of this study is to analyze the reticulocyte parameters (classical and research parameters) acquired by the Beckman Coulter GEN'S blood counter (GEN'S; Brea, CA, USA) to establish the "reticulocyte profile" characteristics of patients with anemia of chronic disease (ACD). The reticulocyte parameters and profile provided by the GEN'S were studied in 38 anemic patients who fulfilled the diagnostic criteria for the ACD, and the results were compared with those of 38 healthy controls in a multivariate statistical analysis using the Student t-test and the receiver operating characteristics (ROC) curve analysis.Statistically significant (P <.05) differences between the 2 population groups were observed in several of the reticulocyte parameters provided by the GEN'S: mean volume of the reticulocyte population (MRV) (high), percentage of high light scatter reticulocytes HLR% (high), mean volume of the whole sphered red cell and reticulocyte population (MSCV) (high) MCV-MSCV (low) with the highest diagnostic value, as measured by the area under the ROC curve (>0.9), for the IRF (high) and the reticulocyte population data: mean channel scatter retics (high) and the mean channel conductivity retics (high). This study establishes the reticulocyte parameters and reticulocyte profile as provided by the GEN'S and characteristic of patients with ACD as compared with normal subjects. This should provide the basis for further studies comparing the reticulocyte profile of patients with ACD with those found in other types of anemia.

  2. [Pathophysiology, diagnosis and treatment of anemia].

    PubMed

    Ozawa, Keiya

    2008-03-01

    Anemia can result from deficient erythropoiesis [aplastic anemia, myelodysplastic syndromes (MDS), iron deficiency anemia, anemia of chronic disease (ACD), thalassemia, megaloblastic anemia, chronic renal failure, hematological malignancies, etc.], excessive RBC destruction [hereditary spherocytosis, inherited enzyme deficiency, hemoglobinopathies, autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), etc.], and blood loss. Based on the measured red cell size(MCV), anemia is classified as microcytic, normocytic, or macrocytic. Iron parameters (serum iron, serum ferritin, etc.), reticulocyte count, bone marrow examination, Coombs test, serum vitamin B12 level, and Ham test are also useful in the differential diagnosis of anemia. Novel treatment of anemia includes lenalidomide for 5q(-)MDS, azacitidine for high-risk MDS, and eculizumab for PNH. Oral iron chelator(deferasirox) developed for the treatment of transfusional iron overload is also very useful for the management of patients with bone marrow failure syndromes.

  3. Artificial intelligence for optimal anemia management in end-stage renal disease.

    PubMed

    Brier, Michael E; Gaweda, Adam E

    2016-08-01

    Computational intelligence for the prediction of hemoglobin to guide the selection of erythropoiesis-stimulating agent dose results in improved anemia management. The models used for the prediction result from the use of individual patient data and help to increase the number of hemoglobin observations within the target range. The benefits of using these modeling techniques appear to be a decrease in erythropoiesis-stimulating agent use and a decrease in the number of transfusions. This study confirms the results of previous smaller studies and suggests that additional beneficial results may be achieved.

  4. Management of renal anemia.

    PubMed

    Peco-Antic, Amira

    2005-01-01

    Normochromic normocytic anemia is common in children with chronic renal failure (CRF) when their glomerular filtration rate is below 35 ml/min/1.73 m2 BSA, but it may develop earlier in some forms of renal disease. An inadequate erythropoiesis due to insufficient erythropoietin synthesis in the kidneys is the main cause of renal anemia. Other reasons include reduced red blood cell lifespan, chronic blood loss, iron deficiency, inhibitors of erythropoiesis, and malnutrition. The presence of anemia contributes to many of the symptoms of uremia, including decreased appetite, decreased energy, poor cardiac function, and poor school performance. Therefore, correction of anemia dramatically improves the life of the child with CRF. Presently, the goal of anemia management is to maintain hematocrit concentrations at 33% to 36% and a hemoglobin concentration of at least 11 g/L. This can be accomplished by intravenous or subcutaneous administration of recombinant erythropoietin (rHuEPO, 100-300 U/kg/week) and iron preparations. If adequate iron stores cannot be maintained with oral therapy (2-3, max 6 mg/kg/day), intravenous iron should be administered. In order to optimize anemia management in children with CRF, future research should be concentrated on the normalization of hemoglobin early in the course of CRF, and the long-term effects on the child's development.

  5. [Heart failure and anemia].

    PubMed

    Reda, S; Motloch, L J; Hoppe, U C

    2013-09-01

    Chronic heart failure has an age-dependent prevalence of 2% and is therefore one of the most frequent diseases in western societies. A reduced hemoglobin concentration according to the definition of the World Health Organization is a common comorbidity affecting more than half of all heart failure patients. Elderly patients, patients suffering from renal impairment and women are more likely to develop anemia but a definitive etiology of anemia is only identified in the minority of cases. Anemia is associated with a poor clinical status and a greater risk of hospitalization and is a predictive factor for increased mortality. The incidence of anemia appears to increase with a poorer functional class. Intravenous iron therapy improves the exercise capacity in patients with systolic heart failure and iron deficiency and is currently being recommended for patients with persistent symptoms despite optimal medical and device therapy. However, erythropoietin-stimulating agents as a treatment for anemia in chronic heart failure have failed to improve clinical outcome in a large randomized trial. In patients with heart failure but with maintained ejection fraction, anemia is also associated with a poor prognosis. Specific therapeutic recommendations for these patients are still not available.

  6. A novel Alzheimer disease locus located near the gene encoding tau protein.

    PubMed

    Jun, G; Ibrahim-Verbaas, C A; Vronskaya, M; Lambert, J-C; Chung, J; Naj, A C; Kunkle, B W; Wang, L-S; Bis, J C; Bellenguez, C; Harold, D; Lunetta, K L; Destefano, A L; Grenier-Boley, B; Sims, R; Beecham, G W; Smith, A V; Chouraki, V; Hamilton-Nelson, K L; Ikram, M A; Fievet, N; Denning, N; Martin, E R; Schmidt, H; Kamatani, Y; Dunstan, M L; Valladares, O; Laza, A R; Zelenika, D; Ramirez, A; Foroud, T M; Choi, S-H; Boland, A; Becker, T; Kukull, W A; van der Lee, S J; Pasquier, F; Cruchaga, C; Beekly, D; Fitzpatrick, A L; Hanon, O; Gill, M; Barber, R; Gudnason, V; Campion, D; Love, S; Bennett, D A; Amin, N; Berr, C; Tsolaki, Magda; Buxbaum, J D; Lopez, O L; Deramecourt, V; Fox, N C; Cantwell, L B; Tárraga, L; Dufouil, C; Hardy, J; Crane, P K; Eiriksdottir, G; Hannequin, D; Clarke, R; Evans, D; Mosley, T H; Letenneur, L; Brayne, C; Maier, W; De Jager, P; Emilsson, V; Dartigues, J-F; Hampel, H; Kamboh, M I; de Bruijn, R F A G; Tzourio, C; Pastor, P; Larson, E B; Rotter, J I; O'Donovan, M C; Montine, T J; Nalls, M A; Mead, S; Reiman, E M; Jonsson, P V; Holmes, C; St George-Hyslop, P H; Boada, M; Passmore, P; Wendland, J R; Schmidt, R; Morgan, K; Winslow, A R; Powell, J F; Carasquillo, M; Younkin, S G; Jakobsdóttir, J; Kauwe, J S K; Wilhelmsen, K C; Rujescu, D; Nöthen, M M; Hofman, A; Jones, L; Haines, J L; Psaty, B M; Van Broeckhoven, C; Holmans, P; Launer, L J; Mayeux, R; Lathrop, M; Goate, A M; Escott-Price, V; Seshadri, S; Pericak-Vance, M A; Amouyel, P; Williams, J; van Duijn, C M; Schellenberg, G D; Farrer, L A

    2016-01-01

    APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe

  7. A NOVEL ALZHEIMER DISEASE LOCUS LOCATED NEAR THE GENE ENCODING TAU PROTEIN

    PubMed Central

    Jun, Gyungah; Ibrahim-Verbaas, Carla A.; Vronskaya, Maria; Lambert, Jean-Charles; Chung, Jaeyoon; Naj, Adam C.; Kunkle, Brian W.; Wang, Li-San; Bis, Joshua C.; Bellenguez, Céline; Harold, Denise; Lunetta, Kathryn L.; Destefano, Anita L.; Grenier-Boley, Benjamin; Sims, Rebecca; Beecham, Gary W.; Smith, Albert V.; Chouraki, Vincent; Hamilton-Nelson, Kara L.; Ikram, M. Arfan; Fievet, Nathalie; Denning, Nicola; Martin, Eden R.; Schmidt, Helena; Kamatani, Yochiro; Dunstan, Melanie L; Valladares, Otto; Laza, Agustin Ruiz; Zelenika, Diana; Ramirez, Alfredo; Foroud, Tatiana M.; Choi, Seung-Hoan; Boland, Anne; Becker, Tim; Kukull, Walter A.; van der Lee, Sven J.; Pasquier, Florence; Cruchaga, Carlos; Beekly, Duane; Fitzpatrick, Annette L.; Hanon, Oliver; Gill, Michael; Barber, Robert; Gudnason, Vilmundur; Campion, Dominique; Love, Seth; Bennett, David A.; Amin, Najaf; Berr, Claudine; Tsolaki, Magda; Buxbaum, Joseph D.; Lopez, Oscar L.; Deramecourt, Vincent; Fox, Nick C; Cantwell, Laura B.; Tárraga, Lluis; Dufouil, Carole; Hardy, John; Crane, Paul K.; Eiriksdottir, Gudny; Hannequin, Didier; Clarke, Robert; Evans, Denis; Mosley, Thomas H.; Letenneur, Luc; Brayne, Carol; Maier, Wolfgang; De Jager, Philip; Emilsson, Valur; Dartigues, Jean-François; Hampel, Harald; Kamboh, M. Ilyas; de Bruijn, Renee F.A.G.; Tzourio, Christophe; Pastor, Pau; Larson, Eric B.; Rotter, Jerome I.; O’Donovan, Michael C; Montine, Thomas J.; Nalls, Michael A.; Mead, Simon; Reiman, Eric M.; Jonsson, Palmi V.; Holmes, Clive; St George-Hyslop, Peter H.; Boada, Mercè; Passmore, Peter; Wendland, Jens R.; Schmidt, Reinhold; Morgan, Kevin; Winslow, Ashley R.; Powell, John F; Carasquillo, Minerva; Younkin, Steven G.; Jakobsdóttir, Jóhanna; Kauwe, John SK; Wilhelmsen, Kirk C.; Rujescu, Dan; Nöthen, Markus M; Hofman, Albert; Jones, Lesley; Haines, Jonathan L.; Psaty, Bruce M.; Van Broeckhoven, Christine; Holmans, Peter; Launer, Lenore J.; Mayeux, Richard; Lathrop, Mark; Goate, Alison M.; Escott-Price, Valentina; Seshadri, Sudha; Pericak-Vance, Margaret A.; Amouyel, Philippe; Williams, Julie; van Duijn, Cornelia M.; Schellenberg, Gerard D.; Farrer, Lindsay A.

    2015-01-01

    APOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer’s Project (IGAP) Consortium in APOE ε4+ (10,352 cases and 9,207 controls) and APOE ε4− (7,184 cases and 26,968 controls) subgroups as well as in the total sample testing for interaction between a SNP and APOE ε4 status. Suggestive associations (P<1x10−4) in stage 1 were evaluated in an independent sample (stage 2) containing 4,203 subjects (APOE ε4+: 1,250 cases and 536 controls; APOE ε4-: 718 cases and 1,699 controls). Among APOE ε4− subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 datasets (best SNP, rs2732703, P=5·8x10−9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100 kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4− subjects (MS4A6A/MS4A4A/ MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6x10−7) is noteworthy because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3x10−8), frontal cortex (P≤1.3x10−9), and temporal cortex (P≤1.2x10−11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively

  8. Major hematologic diseases in the developing world- new aspects of diagnosis and management of thalassemia, malarial anemia, and acute leukemia.

    PubMed

    Greenberg, P L; Gordeuk, V; Issaragrisil, S; Siritanaratkul, N; Fucharoen, S; Ribeiro, R C

    2001-01-01

    The three presentations in this session encompass clinical, pathophysiological and therapeutic aspects of hematologic diseases which impact most heavily on developing world countries. Dr. Victor Gordeuk discusses new insights regarding the multi-faceted pathogenesis of anemia in the complicated malaria occurring in Africa. He describes recent investigations indicating the possible contribution of immune dysregulation to this serious complication and the implications of these findings for disease management. Dr. Surapol Issaragrisil and colleagues describe epidemiologic and clinical characteristics of the thalassemic syndromes. In addition to being considered a major health problem in Southeast Asia, the migration throughout the world of people from this region has caused the disease to have global impact. A unique thalassemia variant, Hb Ebeta-thalassemia, with distinctive clinical features, has particular relevance for this demographic issue. Special focus will be reported regarding recent prenatal molecular screening methods in Thailand which have proven useful for early disease detection and disease control strategies. Dr. Raul Ribeiro describes a clinical model for providing effective treatment for a complex malignancy (childhood acute lymphoblastic leukemia) in countries with limited resources. With the multidisciplinary approach in Central American of the joint venture between St. Jude Children's Research Hospital International Outreach Program and indigenous health care personnel, major therapeutic advances for this disease have been achieved. Given the major demographic population shifts occurring worldwide, these illnesses also have important clinical implications globally. These contributions demonstrate that lessons learned within countries of disease prevalence aid our understanding and management of a number of disorders prominently seen in developed countries. They will show how effective partnerships between hematologists in more and less developed

  9. The role of ferric carboxymaltose in the treatment of iron deficiency anemia in patients with gastrointestinal disease

    PubMed Central

    Koduru, Pramoda; Abraham, Bincy P.

    2016-01-01

    Iron deficiency anemia (IDA) is the most common form of nutritional anemia worldwide. Iron plays a pivotal role in vital functioning of almost every organ system. IDA affects both physical and psychological functioning of humans. Oral iron is considered as first-line therapy for the treatment of IDA due to low cost, good safety profile and ease of administration. However, the absorption of oral iron is affected by several factors and incidence of gastrointestinal side effects can lead to lack of adherence to therapy as well as poor efficacy. This has led to the emergence of intravenous iron therapy which is clearly superior to oral iron with higher increment of hemoglobin levels and rapid replenishment of iron stores. Ferric carboxymaltose (FCM) is a novel non-dextran intravenous iron form which has been approved for use in patients with iron deficiency who have had inadequate response to oral iron therapy, intolerance to oral iron, or nondialysis-dependent chronic kidney disease. The safety and efficacy of using FCM for the treatment of IDA has been demonstrated in several clinical trials. One dose can provide a large amount of iron and has a very short infusion time. It should be considered as first-line therapy in patients with active inflammation like inflammatory bowel disease when gastrointestinal absorption of oral iron may be compromised. It should also be given to patients who have inadequate response to oral iron therapy. It has been shown to be noninferior to other intravenous iron formulations with a good safety profile and produced fewer anaphylactic reactions. PMID:26770269

  10. Anemia of inflammation.

    PubMed

    Roy, Cindy N

    2010-01-01

    Inflammation arising from various etiologies, including infection, autoimmune disorders, chronic diseases, and aging, can promote anemia. The anemia of inflammation (AI) is most often normocytic and normochromic and is usually mild. Characteristic changes in systemic iron handling, erythrocyte production, and erythrocyte life span all contribute to AI. The preferred treatment is directed at the underlying disease. However, when the inflammatory insult is intractable, or the cause has not been diagnosed, there are limited options for treatment of AI. Because anemia is a comorbid condition that is associated with poor outcomes in various chronic disease states, understanding its pathogenesis and developing new tools for its treatment should remain a priority. Hepcidin antimicrobial peptide has taken center stage in recent years as a potent modulator of iron availability. As the technology for quantitative hepcidin analysis improves, hepcidin's role in various disease states is also being revealed. Recent insights concerning the regulatory pathways that modify hepcidin expression have identified novel targets for drug development. As the field advances with such therapeutics, the analysis of the impact of normalized hemoglobin on disease outcomes will confirm whether anemia is a reversible independent contributor to the morbidity and mortality associated with inflammatory diseases.

  11. Association analysis revealed one susceptibility locus for vitiligo with immune-related diseases in the Chinese Han population.

    PubMed

    Li, Shu; Yao, Weiyi; Pan, Qian; Tang, Xianfa; Zhao, Suli; Wang, Wenjun; Zhu, Zhengwei; Gao, Jinping; Sheng, Yujun; Zhou, Fusheng; Zheng, Xiaodong; Zuo, Xianbo; Sun, Liangdan; Zhang, Anping

    2015-07-01

    Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other immune-related diseases. However, there is no reported study on the associations between immune susceptibility polymorphisms and the risk of vitiligo with immune-related diseases. The aim of this study was to evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at 18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844), 12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33 (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune-related diseases in the Chinese Han population. All SNPs were genotyped in 552 patients with vitiligo-associated immune-related diseases and 1656 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated immune-related diseases (autoimmune diseases and allergic diseases) (P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the rs2456973 C allele was also significantly associated with early-onset vitiligo by comparing with controls (P = 0.0001) and in the case-only analysis (P = 0.0114). We confirmed that 12q13.2 was an important candidate locus for vitiligo with immune-related diseases (autoimmune diseases and allergic diseases) and affected disease phenotypes with early onset.

  12. Fanconi anemia: a model disease for studies on human genetics and advanced therapeutics.

    PubMed

    Bogliolo, Massimo; Surrallés, Jordi

    2015-08-01

    Fanconi anemia (FA) is characterized by bone marrow failure, malformations, and chromosome fragility. We review the recent discovery of FA genes and efforts to develop genetic therapies for FA in the last five years. Because current data exclude FANCM as an FA gene, 15 genes remain bona fide FA genes and three (FANCO, FANCR and FANCS) cause an FA like syndrome. Monoallelic mutations in 6 FA associated genes (FANCD1, FANCJ, FANCM, FANCN, FANCO and FANCS) predispose to breast and ovarian cancer. The products of all these genes are involved in the repair of stalled DNA replication forks by unhooking DNA interstrand cross-links and promoting homologous recombination. The genetic characterization of patients with FA is essential for developing therapies, including hematopoietic stem cell transplantation from a savior sibling donor after embryo selection, gene therapy, or genome editing using genetic recombination or engineered nucleases. Newly acquired knowledge about FA promises to provide therapeutic strategies in the near future.

  13. A cluster of four receptor-like genes resides in the Vf locus that confers resistance to apple scab disease.

    PubMed

    Xu, Mingliang; Korban, Schuyler S

    2002-12-01

    The Vf locus, derived from the crabapple species Malus floribunda 821, confers resistance to five races of the fungal pathogen Venturia inaequalis, the causal agent of apple scab disease. In our previous research, the Vf locus was restricted to a BAC contig of approximately 290 kb covered by five overlapping BAC clones. Here, we report on cloning of the resistance gene(s) present in the Vf BAC contig using a highly reliable and straightforward approach. This approach relies on hybridization of labeled cDNAs to amplified inserts of subclones derived from BAC inserts, followed by recovery of full-size transcripts by rapid amplification of cDNA ends (RACE). A cluster of four resistance paralogs (Vfa1, Vfa2, Vfa3, and Vfa4) was identified in the Vf locus. Vfa1, Vfa2 and Vfa4 had no introns and are predicted to encode proteins characterized with extracellular leucine-rich repeats (LRRs) and transmembrane (TM) domains. However, Vfa3 contains an insertion of 780 bp at the end of the LRR motif, resulting in multiple truncated transcripts. Comparison of Vfa1, Vfa2, and Vfa4 paralogs revealed a high degree of overall homology in their deduced amino acid sequences, while divergences were mainly restricted within LRR domains, including variable LRR units, numerous amino acid substitutions, and several residue deletions/duplications. Differential expression profiles among the four paralogs were observed during leaf development. Vfa1, Vfa2, and Vfa3 were active in immature leaves, but slightly expressed in mature leaves, while Vfa4 was active in immature leaves and was highly expressed in mature leaves.

  14. A cluster of four receptor-like genes resides in the Vf locus that confers resistance to apple scab disease.

    PubMed Central

    Xu, Mingliang; Korban, Schuyler S

    2002-01-01

    The Vf locus, derived from the crabapple species Malus floribunda 821, confers resistance to five races of the fungal pathogen Venturia inaequalis, the causal agent of apple scab disease. In our previous research, the Vf locus was restricted to a BAC contig of approximately 290 kb covered by five overlapping BAC clones. Here, we report on cloning of the resistance gene(s) present in the Vf BAC contig using a highly reliable and straightforward approach. This approach relies on hybridization of labeled cDNAs to amplified inserts of subclones derived from BAC inserts, followed by recovery of full-size transcripts by rapid amplification of cDNA ends (RACE). A cluster of four resistance paralogs (Vfa1, Vfa2, Vfa3, and Vfa4) was identified in the Vf locus. Vfa1, Vfa2 and Vfa4 had no introns and are predicted to encode proteins characterized with extracellular leucine-rich repeats (LRRs) and transmembrane (TM) domains. However, Vfa3 contains an insertion of 780 bp at the end of the LRR motif, resulting in multiple truncated transcripts. Comparison of Vfa1, Vfa2, and Vfa4 paralogs revealed a high degree of overall homology in their deduced amino acid sequences, while divergences were mainly restricted within LRR domains, including variable LRR units, numerous amino acid substitutions, and several residue deletions/duplications. Differential expression profiles among the four paralogs were observed during leaf development. Vfa1, Vfa2, and Vfa3 were active in immature leaves, but slightly expressed in mature leaves, while Vfa4 was active in immature leaves and was highly expressed in mature leaves. PMID:12524365

  15. eQTL analysis links inflammatory bowel disease associated 1q21 locus to ECM1 gene.

    PubMed

    Repnik, Katja; Potočnik, Uroš

    2016-08-01

    Genome-wide association studies (GWAS) have been highly successful in inflammatory bowel disease (IBD) with 163 confirmed associations so far. We used expression quantitative trait loci (eQTL) mapping to analyze IBD associated regions for which causative gene from the region is still unknown. First, we performed an extensive literature search and in silico analysis of published GWAS in IBD and eQTL studies and extracted 402 IBD associated SNPs assigned to 208 candidate loci, and 9562 eQTL correlations. When crossing GWA and eQTL data we found that for 50 % of loci there is no eQTL gene, while for 31.2 % we can determine one gene, for 11.1 % two genes and for the remaining 7.7 % three or more genes. Based on that we selected loci with one, two, and three or more eQTL genes and analyzed them in peripheral blood lymphocytes and intestine tissue samples of 606 Slovene patients with IBD and in 449 controls. Association analysis of selected SNPs showed statistical significance for three (rs2631372 and rs1050152 on 5q locus and rs13294 on 1q locus) out of six selected SNPs with at least one phenotype. Furthermore, with eQTL analysis of selected chromosomal regions, we confirmed a link between SNP and gene for four (SLC22A5 on 5q, ECM1 on 1q, ORMDL3 on 17q, and PUS10 on 2p locus) out of five selected regions. For 1q21 loci, we confirmed gene ECM1 as the most plausible gene from this region to be involved in pathogenesis of IBD and thereby contributed new eQTL correlation from this genomic region.

  16. Iron Deficiency Anemia in Pregnancy.

    PubMed

    Breymann, Christian

    2015-10-01

    Anemia is a common problem in obstetrics and perinatal care. Any hemoglobin below 10.5 g/dL can be regarded as true anemia regardless of gestational age. Reasons for anemia in pregnancy are mainly nutritional deficiencies, parasitic and bacterial diseases, and inborn red blood cell disorders such as thalassemias. The main cause of anemia in obstetrics is iron deficiency, which has a worldwide prevalence between estimated 20%-80% and consists of a primarily female population. Stages of iron deficiency are depletion of iron stores, iron-deficient erythropoiesis without anemia, and iron deficiency anemia, the most pronounced form of iron deficiency. Pregnancy anemia can be aggravated by various conditions such as uterine or placental bleedings, gastrointestinal bleedings, and peripartum blood loss. In addition to the general consequences of anemia, there are specific risks during pregnancy for the mother and the fetus such as intrauterine growth retardation, prematurity, feto-placental miss ratio, and higher risk for peripartum blood transfusion. Besides the importance of prophylaxis of iron deficiency, the main therapy options for the treatment of pregnancy anemia are oral iron and intravenous iron preparations.

  17. Hemolytic disease of the fetus and newborn with late-onset anemia due to anti-M: a case report and review of the Japanese literature.

    PubMed

    Yasuda, Hiroyasu; Ohto, Hitoshi; Nollet, Kenneth E; Kawabata, Kinuyo; Saito, Shunnichi; Yagi, Yoshihito; Negishi, Yutaka; Ishida, Atsushi

    2014-01-01

    Hemolytic disease of the fetus and newborn (HDFN) attributed to M/N-incompatibility varies from asymptomatic to lethally hydropic. Case reports are rare, and the clinical significance of anti-M is not completely understood. A challenging case of HDFN due to anti-M prompted an investigation of the Japanese literature, in order to characterize the clinical spectrum of M/N-incompatibility pregnancies in Japan and report results to English-language readers. Japanese reports of HDFN attributed to M/N incompatibility were compiled. Abstracted data include maternal antibody titers at delivery, fetal direct antiglobulin test, hemoglobin, total bilirubin, reticulocyte count at birth, and therapeutic interventions. We investigated characteristics of HDFN due to M/N-incompatible pregnancies in Japan after encountering a case of severe HDFN along with late-onset anemia in an infant born to a woman carrying IgG anti-M with a titer of 1. In total, thirty-three babies with HDFN due to anti-M and one due to anti-N have been reported in Japan since 1975. The median maternal antibody titer was 64 at delivery and was 16 or less in 10 of 34 women (29%). Five of 34 babies (15%) were stillborn or died as neonates. Twenty-one of 29 survivors (72%) had severe hemolytic anemia and/or hydrops fetalis. The reticulocyte count of neonates with anemia stayed below the reference interval. Sixteen (55%) developed late-onset anemia and 14 (48%) were transfused with M-negative RBCs. Significant positive correlation (P < .05) between the hemoglobin value and the reticulocyte count within 4 days of birth was obtained in 16 babies with anti-M HDFN. In the Japanese population, 21 of 34 cases of M/N-incompatible HDFN (72%) have manifested as severe hemolytic anemia and/or hydrops fetalis. Low reticulocyte count in neonates with late-onset anemia is consistent with suppressed erythropoiesis due to anti-M.

  18. Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia.

    PubMed

    Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Townsley, Danielle M; Liu, Baoying; Knickelbein, Jared; Keyvanfar, Keyvan; Dumitriu, Bogdan; Ito, Sawa; Kajigaya, Sachiko; Taylor, James G; Kaplan, Mariana J; Nussenblatt, Robert B; Barrett, A John; O'Shea, John; Young, Neal S

    2016-02-15

    Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4(+) and CD8(+) T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8(+) TSCM frequency was significantly increased in AA compared with healthy controls. An increased CD8(+) TSCM frequency at diagnosis was associated with responsiveness to immunosuppressive therapy, and an elevated CD8(+) TSCM population after immunosuppressive therapy correlated with treatment failure or relapse in AA patients. IFN-γ and IL-2 production was significantly increased in various CD8(+) and CD4(+) T cell subsets in AA patients, including CD8(+) and CD4(+) TSCMs. CD8(+) TSCM frequency was also increased in patients with autoimmune uveitis or sickle cell disease. A positive correlation between CD4(+) and CD8(+) TSCM frequencies was found in AA, autoimmune uveitis, and systemic lupus erythematosus. Evaluation of PD-1, CD160, and CD244 expression revealed that TSCMs were less exhausted compared with other types of memory T cells. Our results suggest that the CD8(+) TSCM subset is a novel biomarker and a potential therapeutic target for AA.

  19. Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia

    PubMed Central

    Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Townsley, Danielle M.; Liu, Baoying; Knickelbein, Jared; Keyvanfar, Keyvan; Dumitriu, Bogdan; Ito, Sawa; Kajigaya, Sachiko; Taylor, James G.; Kaplan, Mariana J.; Nussenblatt, Robert B.; Barrett, A. John; O’Shea, John; Young, Neal S.

    2015-01-01

    Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4+ and CD8+ T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8+ TSCM frequency was significantly increased in AA compared with healthy controls. An increased CD8+ TSCM frequency at diagnosis was associated with responsiveness to immunosuppressive therapy, and an elevated CD8+ TSCM population after immunosuppressive therapy correlated with treatment failure or relapse in AA patients. IFN-γ and IL-2 production was significantly increased in various CD8+ and CD4+ T cell subsets in AA patients, including CD8+ and CD4+ TSCMs. CD8+ TSCM frequency was also increased in patients with autoimmune uveitis or sickle cell disease. A positive correlation between CD4+ and CD8+ TSCM frequencies was found in AA, autoimmune uveitis, and systemic lupus erythematosus. Evaluation of PD-1, CD160, and CD244 expression revealed that TSCMs were less exhausted compared with other types of memory T cells. Our results suggest that the CD8+ TSCM subset is a novel biomarker and a potential therapeutic target for AA. PMID:26764034

  20. Mapping of the chromosome 1p36 region surrounding the Charcot-Marie-Tooth disease type 2A locus

    SciTech Connect

    Denton, P.; Gere, S.; Wolpert, C.

    1994-09-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy. Although CMT2 is clinically indistinguishable from CMT1, the two forms can be differentiated by pathological and neurophysiological methods. We have established one locus, CMT2A on chromosome 1p36, and have established genetic heterogeneity. This locus maps to the region of the deletions associated with neuroblastoma. We have now identified an additional 11 CMT2 families. Three families are linked to chromosome 1p36 while six families are excluded from this region. Another six families are currently under analysis and collection. To date the CMT2A families represent one third of those CMT2 families examined. We have established a microdissection library of the 1p36 region which is currently being characterized for microsatellite repeats and STSs using standard hybridization techniques and a modified degenerate primer method. In addition, new markers (D1S253, D1S450, D1S489, D1S503, GATA27E04, and GATA4H04) placed in this region are being mapped using critical recombinants in the CEPH reference pedigrees. Fluorescent in situ hybridization (FISH) has been used to confirm mapping. A YAC contig is being assembled from the CEPH megabase library using STSs to isolate key YACs which are extended by vectorette end clone and Alu-PCR. These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrates further heterogeneity in the CMT phenotype.

  1. Types of Hemolytic Anemia

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Hemolytic Anemia There are many types of hemolytic anemia. The ... the condition, but you develop it. Inherited Hemolytic Anemias With inherited hemolytic anemias, one or more of ...

  2. What Causes Anemia?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Causes Anemia? The three main causes of anemia are: Blood ... the blood and can lead to anemia. Aplastic Anemia Some infants are born without the ability to ...

  3. Anemia (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Anemia KidsHealth > For Teens > Anemia Print A A A ... Getting Enough Iron en español Anemia What Is Anemia? Lots of teens are tired. With all the ...

  4. What Is Aplastic Anemia?

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Aplastic Anemia? Aplastic anemia (a-PLAS-tik uh-NEE-me-uh) is ... heart, heart failure , infections, and bleeding. Severe aplastic anemia can even cause death. Overview Aplastic anemia is ...

  5. Study of large inbred Friedreich ataxia families reveals a recombination between D9S15 and the disease locus

    SciTech Connect

    Belal, S.; Ben Hamida, C.; Hentati, F.; Ben Hamida, M. ); Panayides, K.; Ioannou, P.; MIddleton, L.T. ); Sirugo, G.; Koenig, S.; Mandel, J.L ); Beckmann, J. )

    1992-12-01

    Friedreich ataxia is a neurodegenerative disorder with autosomal recessive inheritance. Precise linkage mapping of the Friedreich ataxia locus (FRDA) in 9q13-q21 should lead to the isolation of the defective gene by positional cloning. The two closest DNA markers, D9S5 and D9S15, show very tight linkage to FRDA, making difficult the ordering of the three loci. The authors present a linkage study of three large Friedreich ataxia families of Tunisian origin, with several multiallelic markers around D9S5 and D9S15. Haplotype data were used to investigate genetic homogeneity of the disease in these geographically related families. A meiotic recombination was found in a nonaffected individual, which excludes a 150-kb segment, including D9S15, as a possible location for the Freidreich ataxia gene and which should orient the search in the D9S5 region. 16 refs., 1 fig., 1 tab.

  6. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L.

    PubMed

    Patel, Sheetal; Monemian, Seyed; Khalid, Ayesha; Dosik, Harvey

    2011-01-01

    Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  7. Parenteral iron use in the management of anemia in end-stage renal disease patients.

    PubMed

    Bailie, G R; Johnson, C A; Mason, N A

    2000-01-01

    Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

  8. A 2-month-old boy with hemolytic anemia and reticulocytopenia following intravenous immunoglobulin therapy for Kawasaki disease: a case report and literature review

    PubMed Central

    Kim, Na Yeon; Kim, Joon Hwan; Park, Jin Suk; Kim, Soo Hyun; Cho, Yeon Kyung; Cha, Dong Hyun; Kim, Ki Eun; Kang, Myung Suh; Lim, Kyung Ah

    2016-01-01

    Herein, we report a rare case of hemolytic anemia with reticulocytopenia following intravenous immunoglobulin therapy in a young infant treated for Kawasaki disease. A 2-month-old boy presented with fever lasting 3 days, conjunctival injection, strawberry tongue, erythematous edema of the hands, and macular rash, symptoms and signs suggestive of incomplete Kawasaki disease. His fever resolved 8 days after treatment with aspirin and high dose infusion of intravenous immunoglobulin. The hemoglobin and hematocrit decreased from 9.7 g/dL and 27.1% to 7.4 g/dL and 21.3%, respectively. The patient had normocytic hypochromic anemia with anisocytosis, poikilocytosis, immature neutrophils, and nucleated red blood cells. The direct antiglobulin test result was positive, and the reticulocyte count was 1.39%. The patient had an uneventful recovery. However, reticulocytopenia persisted 1 month after discharge. PMID:28018448

  9. Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn’s Disease Patients and Unaffected First-Degree Relatives

    PubMed Central

    Gloux, Karine; Anba-Mondoloni, Jamila

    2016-01-01

    Crohn’s disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn’s disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn’s disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn’s disease. PMID:26824357

  10. Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn's Disease Patients and Unaffected First-Degree Relatives.

    PubMed

    Gloux, Karine; Anba-Mondoloni, Jamila

    2016-01-01

    Crohn's disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn's disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn's disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn's disease.

  11. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

    PubMed

    Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

    2011-11-01

    Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD.

  12. A clinical case of chicken infectious anemia disease and virus DNA detection in naturally infected broilers in Greece.

    PubMed

    Bougiouklis, P A; Sofia, M; Brellou, G; Georgopoulou, I; Billinis, C; Vlemmas, I

    2007-06-01

    In this study, chicken infectious anemia virus (CIAV) DNA was detected from 12-day-old broilers. Clinical history showed that the clinical features were diarrhea, blue wing disease, depression, and death. Necropsy findings were pale liver, severe atrophy of bursa of Fabricius and thymus, and discoloration of the bone marrow as well as hemorrhages subcutaneously and a few in skeletal muscles. The majority of the necropsied broilers had developed gangrenous dermatitis. Histopathology showed hypoplasia of bone marrow and depletion of lymphocytes in spleen, bursa, and subcapsular thymic cortex. Karyorrhexis of lymphocytes was scattered in the thymic cortex and most pronounced in the bursal follicles. Eosinophilic intranuclear inclusion bodies were mainly located in lymphocytes of thymus, with a few in hemopoietic cells of bone marrow. CIAV DNA was detected by polymerase chain reaction from bursa, thymus, and bone marrow. A virus strain was detected and genetically characterized in 639 base pairs of VP1 gene. Phylogenetic analysis revealed that the Greek isolate was clustered together with isolates from Alabama, China, Slovenia, and Bangladesh.

  13. Intravenous iron dextran as a component of anemia management in chronic kidney disease: a report of safety and efficacy.

    PubMed

    Yessayan, Lenar; Sandhu, Ankur; Besarab, Anatole; Yessayan, Alexy; Frinak, Stan; Zasuwa, Gerard; Yee, Jerry

    2013-01-01

    Objective. We aimed to demonstrate safety and efficacy of intravenous (IV) low molecular weight iron dextran (LMWID) during treatment of anemic stage 3 and 4 chronic kidney disease (CKD) patients. Methods. Efficacy data was obtained by retrospective chart review of 150 consecutively enrolled patients. Patients were assigned per protocol to oral or IV iron, with IV iron given to those with lower iron stores and/or hemoglobin. Iron and darbepoetin were administered to achieve and maintain hemoglobin at 10-12 g/dL. Efficacy endpoints were mean hemoglobin and change in iron indices approximately 30 and 60 days after enrollment. Safety data was obtained by retrospective review of reported adverse drug events (ADEs) following 1699 infusions of LMWID (0.5-1.0 g). Results. Mean hemoglobin, iron saturation, and ferritin increased significantly from baseline to 60 days in patients assigned to LMWID (hemoglobin: 11.3 versus 9.4 g/dL; iron saturation: 24% versus 12.9%; ferritin: 294.7 versus 134.7 ng/mL; all P  values < 0.0001). Iron stores and hemoglobin were maintained in the group assigned to oral iron. Of 1699 iron dextran infusions, three ADEs occurred. Conclusions. Treatment of anemia in CKD stages 3 and 4 with LMWID and darbepoetin is efficacious. The serious ADE rate was 0.06% per infusion.

  14. Ferumoxytol: a new intravenous iron preparation for the treatment of iron deficiency anemia in patients with chronic kidney disease.

    PubMed

    Schwenk, Michael H

    2010-01-01

    Ferumoxytol is an intravenous iron preparation for treatment of the anemia of chronic kidney disease (CKD). It is a carbohydrate-coated, superparamagnetic iron oxide nanoparticle. Because little free iron is present in the preparation, doses of 510 mg have been administered safely in as little as 17 seconds. Two prospective, randomized studies compared two doses of ferumoxytol 510 mg given in 5 +/- 3 days with 3 weeks of oral iron 200 mg/day (as ferrous fumarate) in anemic patients with CKD. One study enrolled 304 patients with stages 1-5 CKD (predialysis), and the other study enrolled 230 patients with stage 5D CKD (undergoing hemodialysis). In both studies, a greater increase in hemoglobin level from baseline to end of study (day 35) was noted in patients who received ferumoxytol compared with those who received oral iron (mean +/- SD 0.82 +/- 1.24 vs 0.16 +/- 1.02 g/dl in patients with stages 1-5 CKD and 1.02 +/- 1.13 vs 0.46 +/- 1.06 g/dl in patients with stage 5D CKD, p<0.001). A greater proportion of both predialysis and hemodialysis patients who received ferumoxytol had hemoglobin level increases from baseline of 1 g/dl or more compared with those who received oral iron (p<0.001). In a prospective, double-blind, crossover study of more than 700 patients with CKD stages 1-5D that compared the safety of ferumoxytol with normal saline injection, the rates of treatment-related adverse events were 5.2% and 4.5%, respectively. Serious treatment-related adverse events were seen in one patient in each treatment group. The most common adverse events with ferumoxytol occurred at the injection site (bruising, pain, swelling, erythema). Dizziness, nausea, pruritus, headache, and fatigue occurred in less than 2% of patients receiving ferumoxytol, with a similar frequency noted after administration of normal saline. In short-term studies, intravenous ferumoxytol was safely and rapidly administered, and was more effective than oral iron therapy in increasing hemoglobin

  15. Bed bugs reproductive life cycle in the clothes of a patient suffering from Alzheimer's disease results in iron deficiency anemia.

    PubMed

    Sabou, Marcela; Imperiale, Delphine Gallo; Andrès, Emmanuel; Abou-Bacar, Ahmed; Foeglé, Jacinthe; Lavigne, Thierry; Kaltenbach, Georges; Candolfi, Ermanno

    2013-01-01

    We report the case of an 82-year-old patient, hospitalized for malaise. Her clothes were infested by numerous insects and the entomological analysis identified them as being Cimex lectularius (bed bugs). The history of the patient highlighted severe cognitive impairment. The biological assessment initially showed a profound microcytic, aregenerative, iron deficiency anemia. A vitamin B12 deficiency due to pernicious anemia (positive intrinsic factor antibodies) was also highlighted, but this was not enough to explain the anemia without macrocytosis. Laboratory tests, endoscopy and a CT scan eliminated a tumor etiology responsible for occult bleeding. The patient had a mild itchy rash which was linked to the massive colonization by the bed bugs. The C. lectularius bite is most often considered benign because it is not a vector of infectious agents. Far from trivial, a massive human colonization by bed bugs may cause such a hematic depletion that severe microcytic anemia may result.

  16. Coexistence of megaloblastic anemia and iron deficiency anemia in a young woman with chronic lymphocytic thyroiditis.

    PubMed

    Chen, Shih-Hsiang; Hung, Chia-Sui; Yang, Chao-Ping; Lo, Fu-Sung; Hsu, Hsun-Hui

    2006-10-01

    Pernicious anemia is a megaloblastic anemia caused by vitamin B12 deficiency, and is the end-stage of autoimmune gastritis that typically affects persons older than 60 years. It is the most common cause of vitamin B12 deficiency. Pernicious anemia can also be diagnosed concurrently with other autoimmune diseases. We report the occurrence of megaloblastic anemia in a 22-year-old woman with chronic autoimmune thyroiditis for 10.5 years. Recently, she presented with microcytic anemia, and iron deficiency anemia was diagnosed initially. After administration of ferrous sulfate, macrocytic anemia was revealed and vitamin B12 deficiency was detected. Pernicious anemia was highly suspected because of the endoscopic finding of atrophic gastritis, and high titer of antigastric parietal cell antibody, as well as elevated serum gastrin level. After intramuscular injections of hydroxycobalamine 100 microg daily for 10 days, and monthly later, her blood counts returned to normal.

  17. [Hemolytic anemias and vitamin B12 deficieny].

    PubMed

    Dietzfelbinger, Hermann; Hubmann, Max

    2015-08-01

    Hemolytic anemias consist of corpuscular, immun-hemolytic and toxic hemolytic anemias. Within the group of corpuscular hemolytic anemias, except for the paroxysmal nocturnal hemoglobinuria (PNH), all symptoms are caused by underlying heredetiary disorders within the red blood cell membran (hereditary spherocytosis), deficiencies of red cell enzymes (G6PDH- and pyrovatkinase deficiency) or disorders in the hemoglobin molecule (thalassaemia and sickle cell disease). Immune-hemolytic anemias are acquired hemolytic anemias and hemolysis is caused by auto- or allo-antibodies which are directed against red blood cell antigens. They are classified as warm, cold, mixed type or drug-induced hemolytic anemia. Therapy consists of glucocorticoids and other immunsuppressive drugs. Pernicious anemia is the most important vitamin B12 deficiency disorder. Diagnosis relies on cobalamin deficiency and antibodies to intrinsic factor. The management should focus on a possibly life-long replacement treatment with cobalamin.

  18. A radiation hybrid map of human chromosome 11q22-q23 containing the ataxia-telangiectasia disease locus

    SciTech Connect

    Richard, C.W. III; Cox, D.R.; Kapp, L.; Murnane, J. ); Cornelis, F.; Julier, C.; Lathrop, M.; James, M.R. )

    1993-07-01

    The authors describe a high-resolution radiation hybrid map of human chromosome 11q22-q23 containing the ataxia-telangiectasia (AT) disease gene loci. The order and intermarker distances of 32 chromosome 11q22-q23 markers were determined by a multipoint maximum likelihood method analysis of the cosegregation of markers in 100 radiation hybrids. The radiation hybrid map of polymorphic loci was consistent with genetic linkage maps of common markers. Several genes, including [alpha]B-crystallin, adrenal ferrodoxin, CBL2, collagenase, dopamine receptor type 2, neural cell adhesion molecule, progesterone receptor, and stromelysins 1 and 2, were placed in relation to previously ordered, genetically mapped polymorphic loci. Five new markers ([alpha]B-crystallin, adrenal ferrodoxin, CJ52.114, CJ52.3, and D11S535) were ordered within the current published flanking markers for the AT group A and group C disease loci. A candidate AT group D gene (ATDC) identified by Kapp et al. was mapped telomeric to THY1, outside the flanking markers identified by multipoint linkage analysis for the major AT locus. 29 refs., 1 fig., 2 tabs.

  19. Sexuality and sickle cell anemia

    PubMed Central

    Côbo, Viviane de Almeida; Chapadeiro, Cibele Alves; Ribeiro, João Batista; Moraes-Souza, Helio; Martins, Paulo Roberto Juliano

    2013-01-01

    Background Sickle cell disease, the most common hereditary blood disease in the world, is the result of an atypical hemoglobin called S (Hb S) which, when homozygous (Hb SS) is the cause of sickle cell anemia. Changes of puberty, correlated with a delayed growth spurt, begin late in both male and female sickle cell anemia individuals with repercussions on sexuality and reproduction. The objectives of this exploratory and descriptive study were to characterize the development of sexuality in adults with sickle cell anemia by investigating the patient's perception of their sex life, as well as the information they had and needed on this subject. Methods Twenty male and female sickle cell anemia patients treated at the Hemocentro Regional de Uberaba (UFTM) with ages between 19 and 47 years old were enrolled. A socioeconomic questionnaire and a semi-structured interview on sexuality, reproduction and genetic counseling were applied. Results This study shows that the sickle cell anemia patients lacked information on sexuality especially about the risks of pregnancy and the possible inheritance of the disease by their children. Moreover, the sexual life of the patients was impaired due to pain as well as discrimination and negative feelings experienced in close relationships. Conclusion The health care of sickle cell anemia patients should take into account not only the clinical aspects of the disease, but also psychosocial aspects by providing counseling on sexuality, reproduction and genetics, in order to give this population the possibility of a better quality of life. PMID:23741184

  20. Gestational anemia.

    PubMed

    Wahed, F; Latif, S A; Nessa, A; Bhuiyan, M R; Hossain, M B; Akther, A; Mahmud, M M

    2010-07-01

    Gestational anemia is a common public health problem in our country. Most anemia during pregnancy results from an increased need for iron as her body is making more blood. Often dietary supplementation does not provide enough iron to meet the extra needs. Also the growing baby takes all the iron it needs from mother, regardless of how much iron is stored in mother's blood. Gestational Anemia contributed significantly to maternal morbidity and mortality, IUGR, preterm delivery and perinatal morbidity and mortality. A high proportion of women in both industrialized and developing countries become anemic during pregnancy. The most important cause of gestational anemia due to iron deficiency, because high iron requirements during pregnancy are not easily fulfilled by dietary intake. Adequate iron stores can help a pregnant women replace lost red blood cells. So, iron supplementation is strongly recommended for all pregnant women in developing countries. Oral iron intake is the treatment of choice and almost all pregnant women can be treated effectively with oral iron preparation during their pregnancy period.

  1. The Prevalence and Management of Anemia in Chronic Kidney Disease Patients: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

    PubMed Central

    2017-01-01

    Anemia is a common and significant complication of chronic kidney disease (CKD). However, its prevalence and current management status has not been studied thoroughly in Korea. We examined the prevalence of anemia, its association with clinical and laboratory factors, and utilization of iron agents and erythropoiesis stimulating agents using the baseline data from the large-scale CKD cohort in Korea. We defined anemia when hemoglobin level was lower than 13.0 g/dL in males and 12.0 g/dL in females, or received by erythropoiesis stimulating agents. Overall prevalence of anemia was 45.0% among 2,198 non-dialysis CKD patients from stage 1 to 5. Diabetic nephropathy (DN) as a cause, CKD stages, body mass index (BMI), smoking, leukocyte count, serum albumin, iron markers, calcium, and phosphorus concentration were identified as independent risk factors for anemia. Considering the current coverage of Korean National Health Insurance System, only 7.9% among applicable patients were managed by intravenous iron agents, and 42.7% were managed by erythropoiesis stimulating agents. PMID:28049235

  2. Abnormal expression of inflammatory genes in placentas of women with sickle cell anemia and sickle hemoglobin C disease.

    PubMed

    Baptista, Letícia C; Costa, Maria Laura; Ferreira, Regiane; Albuquerque, Dulcinéia M; Lanaro, Carolina; Fertrin, Kleber Y; Surita, Fernanda G; Parpinelli, Mary A; Costa, Fernando F; Melo, Mônica Barbosa de

    2016-10-01

    Sickle cell disease (SCD) is a complex disease that is characterized by the polymerization of deoxyhemoglobin S, altered red blood cell membrane biology, endothelial activation, hemolysis, a procoagulant state, acute and chronic inflammation, and vaso-occlusion. Among the physiological changes that occur during pregnancy, oxygen is consumed by fetal growth, and pregnant women with SCD are more frequently exposed to low oxygen levels. This might lead to red blood cells sickling, and, consequently, to vaso-occlusion. The mechanisms by which SCD affects placental physiology are largely unknown, and chronic inflammation might be involved in this process. This study aimed to evaluate the gene expression profile of inflammatory response mediators in the placentas of pregnant women with sickle cell cell anemia (HbSS) and hemoglobinopathy SC (HbSC). Our results show differences in a number of these genes. For the HbSS group, when compared to the control group, the following genes showed differential expression: IL1RAP (2.76-fold), BCL6 (4.49-fold), CXCL10 (-2.12-fold), CXCR1 (-3.66-fold), and C3 (-2.0-fold). On the other hand, the HbSC group presented differential expressions of the following genes, when compared to the control group: IL1RAP (4.33-fold), CXCL1 (3.05-fold), BCL6 (4.13-fold), CXCL10 (-3.32-fold), C3 (-2.0-fold), and TLR3 (2.38-fold). Taken together, these data strongly suggest a differential expression of several inflammatory genes in both SCD (HbSS and HbSC), indicating that the placenta might become an environment with hypoxia, and increased inflammation, which could lead to improper placental development.

  3. Some epistatic two-locus models of disease. II. The confounding of linkage and association

    PubMed Central

    Hodge, Susan E.; Spence, M. Anne

    1981-01-01

    This paper continues to examine the model discussed in the preceding paper. Specifically, it will be shown how a linkage analysis performed in the presence of a disease-marker association can give rise to erroneous and misleading results. PMID:6941696

  4. Hereditary sideroblastic anemia: pathophysiology and gene mutations.

    PubMed

    Harigae, Hideo; Furuyama, Kazumichi

    2010-10-01

    Sideroblastic anemia is characterized by anemia with the emergence of ring sideroblasts in the bone marrow. Ring sideroblasts are erythroblasts characterized by iron accumulation in perinuclear mitochondria due to impaired iron utilization. There are two forms of sideroblastic anemia, i.e., inherited and acquired sideroblastic anemia. Inherited sideroblastic anemia is a rare and heterogeneous disease caused by mutations of genes involved in heme biosynthesis, iron-sulfur (Fe-S) cluster biogenesis, or Fe-S cluster transport, and mitochondrial metabolism. The most common inherited sideroblastic anemia is X-linked sideroblastic anemia (XLSA) caused by mutations of the erythroid-specific δ-aminolevulinate synthase gene (ALAS2), which is the first enzyme of heme biosynthesis in erythroid cells. Sideroblastic anemia due to SLC25A38 gene mutations, which is a mitochondrial transporter, is the next most common inherited sideroblastic anemia. Other forms of inherited sideroblastic anemia are very rare, and accompanied by impaired function of organs other than hematopoietic tissue, such as the nervous system, muscle, or exocrine glands due to impaired mitochondrial metabolism. Moreover, there are still significant numbers of cases with genetically undefined inherited sideroblastic anemia. Molecular analysis of these cases will contribute not only to the development of effective treatment, but also to the understanding of mitochondrial iron metabolism.

  5. A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.

    PubMed

    Grupe, Andrew; Li, Yonghong; Rowland, Charles; Nowotny, Petra; Hinrichs, Anthony L; Smemo, Scott; Kauwe, John S K; Maxwell, Taylor J; Cherny, Sara; Doil, Lisa; Tacey, Kristina; van Luchene, Ryan; Myers, Amanda; Wavrant-De Vrièze, Fabienne; Kaleem, Mona; Hollingworth, Paul; Jehu, Luke; Foy, Catherine; Archer, Nicola; Hamilton, Gillian; Holmans, Peter; Morris, Chris M; Catanese, Joseph; Sninsky, John; White, Thomas J; Powell, John; Hardy, John; O'Donovan, Michael; Lovestone, Simon; Jones, Lesley; Morris, John C; Thal, Leon; Owen, Michael; Williams, Julie; Goate, Alison

    2006-01-01

    Strong evidence of linkage to late-onset Alzheimer disease (LOAD) has been observed on chromosome 10, which implicates a wide region and at least one disease-susceptibility locus. Although significant associations with several biological candidate genes on chromosome 10 have been reported, these findings have not been consistently replicated, and they remain controversial. We performed a chromosome 10-specific association study with 1,412 gene-based single-nucleotide polymorphisms (SNPs), to identify susceptibility genes for developing LOAD. The scan included SNPs in 677 of 1,270 known or predicted genes; each gene contained one or more markers, about half (48%) of which represented putative functional mutations. In general, the initial testing was performed in a white case-control sample from the St. Louis area, with 419 LOAD cases and 377 age-matched controls. Markers that showed significant association in the exploratory analysis were followed up in several other white case-control sample sets to confirm the initial association. Of the 1,397 markers tested in the exploratory sample, 69 reached significance (P < .05). Five of these markers replicated at P < .05 in the validation sample sets. One marker, rs498055, located in a gene homologous to RPS3A (LOC439999), was significantly associated with Alzheimer disease in four of six case-control series, with an allelic P value of .0001 for a meta-analysis of all six samples. One of the case-control samples with significant association to rs498055 was derived from the linkage sample (P = .0165). These results indicate that variants in the RPS3A homologue are associated with LOAD and implicate this gene, adjacent genes, or other functional variants (e.g., noncoding RNAs) in the pathogenesis of this disorder.

  6. Inborn anemias in mice: (Annual report, 1983-1984)

    SciTech Connect

    Bernstein, S.E.

    1984-09-01

    The hypotranserrinemic-hemochromatosis mutation in mice discovered in our laboratory is an almost exact duplicate of human atransferrinemia. Just as in man, the condition is inherited as a recessive lethal. The disease appears to stem from a congenital deficiency in transferrin. The new mutation arose spontaneously in BALB/c mice and results in death before 12 days of age. It is characterized by stunted growth, low numbers of erythrocytes, hypochromia, and in the absence of jaundice. Treatments with Imferon or other iron preparations were uniformly unsuccessful, but the use of normal mouse serum proved successful as a therapeutic measure. We find that we are able to keep these afflicted mice alive for more than a year with small amounts of normal serum, and transferrin bands are missing on cellulose acetate electrophoresis of serum proteins from affected individuals receiving no treatment. Genetic tests indicated that the new mutation was not an allele of any of the other known iron deficiency anemias in the mouse: sex linked anemia (sla), microcytic anemia (mk), or flexed anemia (f) or any of the members of the hemolytic disease group (sph, sph/sup ha/, nb, or ja). Biochemical and genetic analyses carried out during the past year indicate that the new mutation, tentatively designated hpx is not likely to be a mutation at the transferrin (Trf) locus on Chromosome 9. We observed no unusual serum proteins on cellulose acetate electrophoresis, such as might be expected if the Trf gene had mutated. Moreover, radial immunodiffusion examination and Ouchterlony analysis did not show the presence of smaller molecules (or fragments) with transferrin antigenic specificities. Instead they showed a total loss in serum transferrin. 14 refs., 5 tabs.

  7. Analysis of microsatellite polymorphism around the HLA-B locus in Iranian patients with Behçet's disease.

    PubMed

    Mizuki, N; Yabuki, K; Ota, M; Katsuyama, Y; Ando, H; Nomura, E; Funakoshi, K; Davatchi, F; Chams, H; Nikbin, B; Ghaderi, A A; Ohno, S; Inoko, H

    2002-11-01

    We have previously suggested that in a Japanese population the susceptible locus for Behçet's disease (BD) is HLA-B51 itself. To confirm this finding in another population, we performed HLA class I typing using the PCR-SSP method and analyzed eight polymorphic markers distributed within 1100 kb around the HLA-B gene using automated sequencer and subsequent automated fragment detection by fluorescent-based technology with the DNA samples of 84 Iranian patients with BD and 87 healthy ethnically matched controls. As a result, three microsatellite alleles (MICA-A6, MIB-348, C1-4-1-217) and HLA-B51 were found to be strongly associated with BD. Of these alleles HLA-B51 is the most strongly associated allele. There were no alleles that were increased in allele frequency at any microsatellite loci centromeric of MICA or telomeric of HLA-B51. Therefore, HLA-B51 was confirmed to be by far the most strongly associated gene with BD in an Iranian population.

  8. Response of Iron Deficiency Anemia to Intravenous Iron Sucrose in Pediatric Inflammatory Bowel Disease

    PubMed Central

    2016-01-01

    OBJECTIVES: The objective of this retrospective study was to evaluate the safety and efficacy of intravenous iron sucrose (IS) in iron deficient children with inflammatory bowel disease (IBD) in remission. METHODS: Electronic medical records at a university based pediatric children's hospital were searched for patients in age range 0 to 18 years with diagnosis of IBD and treatment with IS over a 1-year period. Response to IS treatment was assessed by posttreatment changes in ferritin, hemoglobin (Hb), and mean corpuscular volume (MCV). Patients with recorded symptoms of active disease were excluded from analysis of treatment response. RESULTS: Twelve patients were identified by the search criteria, 10 with Crohn's disease (CD), 2 with ulcerative colitis (UC). Data represent 8 patients in remission, 7 with CD and 1 with UC, who received a total of 34 IS infusions. Iron sucrose was administered in cycles of 2 infusions, 2.5 to 3.5 mg/kg/dose (maximum 200 mg), 1 week apart. Mean ferritin increased from 21.4 ± 9.2 to 52.9 ± 10.1 ng/mL (p = 0.0005), Hb from 10.9 ± 0.4 to 11.3 ± 0.3 g/dL (p = 0.02), and MCV from 76.9 ± 2 to 79.4 ± 2 fl (p = 0.006). Iron sucrose treatment normalized ferritin in 6 of 7, Hb in 2 of 8, and MCV in 2 of 5 patients with low pretreatment levels. No adverse effects were recorded. CONCLUSIONS: Two IS infusions of 2.5 to 3.5 mg/kg/dose (maximum 200 mg), given 1 week apart normalized ferritin levels in most pediatric IBD patients in remission without adverse effects. Further studies are needed to determine optimal dosing schedules. PMID:27199624

  9. Added value of hepcidin quantification for the diagnosis and follow-up of anemia-related diseases.

    PubMed

    Lefebvre, Thibaud; Lasocki, Sigismond; Fénéant-Thibault, Martine; Lamy, Pierre-Jean; Cunat, Séverine; Ropert-Bouchet, Madeleine; Aguilar-Martinez, Patricia; Lehmann, Sylvain; Delaby, Constance

    2017-02-01

    Iron homeostasis is based on a strict control of both intestinal iron absorption and iron recycling through reticulo-endothelial system. Hepcidin controls the iron fluxes in order to maintain sufficient iron levels for erythropoietic activities, hemoproteins synthesis or enzymes function, but also to limit its toxic accumulation throughout the body. Hepcidin expression is regulated by various stimuli: inflammation and iron stimulate the production of the peptide, while anemia, erythropoiesis and hypoxia repress its production. Regulation of hepcidin expression is not so simple in complex pathological situations such as hemolytic anemia, cancer or chronic inflammation. Serum hepcidin quantification in association with the diagnostic tests currently available is quite promising for the diagnosis or the follow-up of anemia in those conditions. This study is part of the working group « Clinical interests of hepcidin quantification » of the Société française de biologie clinique.

  10. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia

    PubMed Central

    Lee, Soo Min; Nguyen, Dara; Anand, Marie; Kant, Ritu; Köhncke, Clemens; Lisewski, Ulrike; Roepke, Torsten K.; Hu, Zhaoyang; Abbott, Geoffrey W.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel β subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2─/─ mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis. PMID:26984260

  11. Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients

    PubMed Central

    Saadah, Omar I.; Shaik, Noor Ahmad; Banaganapalli, Babajan; Salama, Mohammed A.; Al-Harthi, Sameer E.; Wang, Jun; Shawoosh, Harbi A.; Alghamdi, Sharifa A.; Bin-Taleb, Yagoub Y.; Alhussaini, Bakr H.; Elango, Ramu; Al-Aama, Jumana Y.

    2015-01-01

    Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22–5.54; P < 0.01). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05–2.28; P = 0.02) and additive (OR = 0.35; 95% CI: 0.17–0.71; P = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0156). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD. PMID:26843707

  12. Vitamin Deficiency Anemia

    MedlinePlus

    Vitamin deficiency anemia Overview By Mayo Clinic Staff Vitamin deficiency anemia is a lack of healthy red blood ... normal amounts of certain vitamins. Vitamins linked to vitamin deficiency anemia include folate, vitamin B-12 and vitamin ...

  13. What Causes Aplastic Anemia?

    MedlinePlus

    ... to aplastic anemia. Examples include Fanconi anemia , Shwachman-Diamond syndrome, dyskeratosis (DIS-ker-ah-TO-sis) congenita, and Diamond-Blackfan anemia. Rate This Content: NEXT >> Featured Video ...

  14. Anemia and Pregnancy

    MedlinePlus

    ... Advocacy Toolkit Home For Patients Blood Disorders Anemia Anemia and Pregnancy Your body goes through significant changes ... becoming anemic. back to top Is Pregnancy-Related Anemia Preventable? Good nutrition is the best way to ...

  15. Folate-deficiency anemia

    MedlinePlus

    ... medlineplus.gov/ency/article/000551.htm Folate-deficiency anemia To use the sharing features on this page, please enable JavaScript. Folate-deficiency anemia is a decrease in red blood cells (anemia) ...

  16. Anemia (For Parents)

    MedlinePlus

    ... a drug or toxin. Anemia From Destruction of Red Blood Cells When the body destroys red blood cells (a ... but can affect all races. continue Anemia From Red Blood Cell Loss Blood loss can cause anemia — whether from ...

  17. Sickle cell anemia - resources

    MedlinePlus

    Resources - sickle cell anemia ... The following organizations are good resources for information on sickle cell anemia : American Sickle Cell Anemia Association -- www.ascaa.org National Heart, Blood, and Lung Institute -- www. ...

  18. Multi-locus genetic risk score predicts risk for Crohn’s disease in Slovenian population

    PubMed Central

    Zupančič, Katarina; Skok, Kristijan; Repnik, Katja; Weersma, Rinse K; Potočnik, Uroš; Skok, Pavel

    2016-01-01

    AIM: To develop a risk model for Crohn’s disease (CD) based on homogeneous population. METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms (SNPs). We generated genetic risk scores (GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve (AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios (LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group. RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk (GRS > 5.54) showed significantly increased odds of developing CD (OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk (GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size (OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76. CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population. PMID:27076762

  19. Parenteral iron compounds: potent oxidants but mainstays of anemia management in chronic renal disease.

    PubMed

    Zager, Richard A

    2006-09-01

    Ferric iron (Fe)-carbohydrate complexes are widely used for treating Fe deficiency in patients who are unable to meet their Fe requirements with oral supplements. Intravenous Fe generally is well tolerated and effective in correcting Fe-deficient states. However, the complexing of Fe to carbohydrate polymers does not block its potent pro-oxidant effects; systemic free radical generation and, possibly, tissue damage may result. The purpose of this review is to (1) underscore the capacity of currently used parenteral Fe formulations to induce oxidative stress, (2) compare the severity of these oxidant reactions with those that result from unshielded Fe salts and with each other, and (3) speculate as to the potential of these agents to induce acute renal cell injury and augment systemic inflammatory responses. The experimental data that are reviewed should not be extrapolated to the clinical setting or be used for clinical decision making. Rather, it is hoped that the information provided herein may have utility for clinical hypothesis generation and, hence, future clinical studies. By so doing, a better understanding of Fe's potential protean effects on patients with renal disease may result.

  20. Iron refractory iron deficiency anemia

    PubMed Central

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U.; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach. PMID:23729726

  1. RPS2, an Arabidopsis disease resistance locus specifying recognition of Pseudomonas syringae strains expressing the avirulence gene avrRpt2.

    PubMed Central

    Kunkel, B N; Bent, A F; Dahlbeck, D; Innes, R W; Staskawicz, B J

    1993-01-01

    A molecular genetic approach was used to identify and characterize plant genes that control bacterial disease resistance in Arabidopsis. A screen for mutants with altered resistance to the bacterial pathogen Pseudomonas syringae pv. tomato (Pst) expressing the avirulence gene avrRpt2 resulted in the isolation of four susceptible rps (resistance to P. syringae) mutants. The rps mutants lost resistance specifically to bacterial strains expressing avrRpt2 as they retained resistance to Pst strains expressing the avirulence genes avrB or avrRpm1. Genetic analysis indicated that in each of the four rps mutants, susceptibility was due to a single mutation mapping to the same locus on chromosome 4. Identification of a resistance locus with specificity for a single bacterial avirulence gene suggests that this locus, designated RPS2, controls specific recognition of bacteria expressing the avirulence gene avrRpt2. Ecotype Wü-0, a naturally occurring line that is susceptible to Pst strains expressing avrRpt2, appears to lack a functional allele at RPS2, demonstrating that there is natural variation at the RPS2 locus among wild populations of Arabidopsis. PMID:8400869

  2. [Pernicious anemia in an adolescent with type 1 diabetes mellitus].

    PubMed

    Carneiro, M; Dumont, C

    2009-04-01

    The most frequent organ-specific autoimmune diseases associated with type 1 diabetes mellitus in children are hypothyroidism and celiac disease. Among adults, other associations exist, notably with pernicious anemia, which is extremely rare in children. We relate the observation of an adolescent with type 1 diabetes mellitus and hypothyroidism, admitted for severe anemia in addition to chronic anemia caused by autoimmune gastritis. Blood cell count showed severe aregenerative anemia with pancytopenia, with signs of non-autoimmune hemolysis. Vitamin B12 levels were low, bone marrow aspiration revealed erythroid hyperplasia, and anti-intrinsic factor antibodies were positive, providing the diagnosis of pernicious anemia. Treatment with intramuscular vitamin B12 produced brisk reticulosis after 6 days, with a subsequent rapid resolution of the anemia. Follow-up of type 1 diabetes mellitus in children requires screening for organ-specific autoimmune diseases; in case of unexplained anemia, autoimmune gastritis must be suggested. It can evolve into pernicious anemia.

  3. Crohn's Disease Risk Alleles on the NOD2 Locus Have Been Maintained by Natural Selection on Standing Variation

    PubMed Central

    Nakagome, Shigeki; Mano, Shuhei; Kozlowski, Lukasz; Bujnicki, Janusz M.; Shibata, Hiroki; Fukumaki, Yasuaki; Kidd, Judith R.; Kidd, Kenneth K.; Kawamura, Shoji; Oota, Hiroki

    2012-01-01

    Risk alleles for complex diseases are widely spread throughout human populations. However, little is known about the geographic distribution and frequencies of risk alleles, which may contribute to differences in disease susceptibility and prevalence among populations. Here, we focus on Crohn's disease (CD) as a model for the evolutionary study of complex disease alleles. Recent genome-wide association studies and classical linkage analyses have identified more than 70 susceptible genomic regions for CD in Europeans, but only a few have been confirmed in non-European populations. Our analysis of eight European-specific susceptibility genes using HapMap data shows that at the NOD2 locus the CD-risk alleles are linked with a haplotype specific to CEU at a frequency that is significantly higher compared with the entire genome. We subsequently examined nine global populations and found that the CD-risk alleles spread through hitchhiking with a high-frequency haplotype (H1) exclusive to Europeans. To examine the neutrality of NOD2, we performed phylogenetic network analyses, coalescent simulation, protein structural prediction, characterization of mutation patterns, and estimations of population growth and time to most recent common ancestor (TMRCA). We found that while H1 was significantly prevalent in European populations, the H1 TMRCA predated human migration out of Africa. H1 is likely to have undergone negative selection because 1) the root of H1 genealogy is defined by a preexisting amino acid substitution that causes serious conformational changes to the NOD2 protein, 2) the haplotype has almost become extinct in Africa, and 3) the haplotype has not been affected by the recent European expansion reflected in the other haplotypes. Nevertheless, H1 has survived in European populations, suggesting that the haplotype is advantageous to this group. We propose that several CD-risk alleles, which destabilize and disrupt the NOD2 protein, have been maintained by natural

  4. Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation.

    PubMed Central

    Cuppens, H; Lin, W; Jaspers, M; Costes, B; Teng, H; Vankeerberghen, A; Jorissen, M; Droogmans, G; Reynaert, I; Goossens, M; Nilius, B; Cassiman, J J

    1998-01-01

    In congenital bilateral absence of the vas deferens patients, the T5 allele at the polymorphic Tn locus in the CFTR (cystic fibrosis transmembrane conductance regulator) gene is a frequent disease mutation with incomplete penetrance. This T5 allele will result in a high proportion of CFTR transcripts that lack exon 9, whose translation products will not contribute to apical chloride channel activity. Besides the polymorphic Tn locus, more than 120 polymorphisms have been described in the CFTR gene. We hypothesized that the combination of particular alleles at several polymorphic loci might result in less functional or even insufficient CFTR protein. Analysis of three polymorphic loci with frequent alleles in the general population showed that, in addition to the known effect of the Tn locus, the quantity and quality of CFTR transcripts and/or proteins was affected by two other polymorphic loci: (TG)m and M470V. On a T7 background, the (TG)11 allele gave a 2.8-fold increase in the proportion of CFTR transcripts that lacked exon 9, and (TG)12 gave a sixfold increase, compared with the (TG)10 allele. T5 CFTR genes derived from patients were found to carry a high number of TG repeats, while T5 CFTR genes derived from healthy CF fathers harbored a low number of TG repeats. Moreover, it was found that M470 CFTR proteins matured more slowly, and that they had a 1.7-fold increased intrinsic chloride channel activity compared with V470 CFTR proteins, suggesting that the M470V locus might also play a role in the partial penetrance of T5 as a disease mutation. Such polyvariant mutant genes could explain why apparently normal CFTR genes cause disease. Moreover, they might be responsible for variation in the phenotypic expression of CFTR mutations, and be of relevance in other genetic diseases. PMID:9435322

  5. Classification of anemia for gastroenterologists

    PubMed Central

    Moreno Chulilla, Jose Antonio; Romero Colás, Maria Soledad; Gutiérrez Martín, Martín

    2009-01-01

    Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia, its morphological classification (microcytic, macrocytic and normocytic) and pathogenic classification (regenerative and hypo regenerative), and integration of these classifications. Interpretation of laboratory tests is included, from the simplest (blood count, routine biochemistry) to the more specific (iron metabolism, vitamin B12, folic acid, reticulocytes, erythropoietin, bone marrow examination and Schilling test). In the text and various algorithms, we propose a hierarchical and logical way to reach a diagnosis as quickly as possible, by properly managing the medical interview, physical examination, appropriate laboratory tests, bone marrow examination, and other complementary tests. The prevalence is emphasized in all sections so that the gastroenterologist can direct the diagnosis to the most common diseases, although the tables also include rare diseases. Digestive diseases potentially causing anemia have been studied in preference, but other causes of anemia have been included in the text and tables. Primitive hematological diseases that cause anemia are only listed, but are not discussed in depth. The last section is dedicated to simplifying all items discussed above, using practical rules to guide diagnosis and medical care with the greatest economy of resources and time. PMID:19787825

  6. Genetic correction of sickle cell anemia and beta-thalassemia: progress and new perspective.

    PubMed

    Perumbeti, Ajay; Malik, Punam

    2010-04-13

    Gene therapy for beta-globinopathies, particularly Beta-thalassemia and sickle cell anemia, holds promise for the future as a definitive corrective approach for these common and debilitating disorders. Correction of the beta-globinopathies using lentivirus vectors carrying the beta- or y-globin genes and elements of the locus control region has now been well established in murine models, and an understanding of "what is required to cure these diseases" has been developed in the first decade of the 21st century. A clinical trial using one such vector has been initiated in France with intriguing results, while other trials are under development. Vector improvements to enhance the safety and efficiency of lentivirus vectors are being explored, while new strategies, including homologous recombination in induced pluripotent cells, for correction of sickle cell anemia have shown proof-of-concept in vitro. Here, a review is provided of the current substantial progress in genetic correction of beta-globin disorders.

  7. Warm autoimmune hemolytic anemia.

    PubMed

    Naik, Rakhi

    2015-06-01

    Warm autoimmune hemolytic anemia (AIHA) is defined as the destruction of circulating red blood cells (RBCs) in the setting of anti-RBC autoantibodies that optimally react at 37°C. The pathophysiology of disease involves phagocytosis of autoantibody-coated RBCs in the spleen and complement-mediated hemolysis. Thus far, treatment is aimed at decreasing autoantibody production with immunosuppression or reducing phagocytosis of affected cells in the spleen. The role of complement inhibitors in warm AIHA has not been explored. This article addresses the diagnosis, etiology, and treatment of warm AIHA and highlights the role of complement in disease pathology.

  8. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses...

  9. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses...

  10. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses...

  11. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses...

  12. 9 CFR 311.34 - Anemia.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Anemia. 311.34 Section 311.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.34 Anemia. Carcasses...

  13. Anti-hepcidin therapy for iron-restricted anemias.

    PubMed

    Nemeth, Elizabeta

    2013-10-24

    In this issue of Blood, Cooke et al demonstrate the potential of a fully human anti-hepcidin antibody as a novel therapeutic for iron-restricted anemias such as anemia of inflammation, cancer, or chronic kidney disease (formerly known as “anemia of chronic diseases”).

  14. Reticulocytosis and anemia are associated with an increased risk of death and stroke in the newborn cohort of the Cooperative Study of Sickle Cell Disease.

    PubMed

    Meier, Emily Riehm; Wright, Elizabeth C; Miller, Jeffery L

    2014-09-01

    Prior analyses of the Cooperative Study of Sickle Cell Disease (CSSCD) newborn cohort identified elevated white blood cell (WBC) count, low baseline hemoglobin and dactylitis between the ages of 1 and 2 years as markers of severe disease. Reticulocytosis was also associated with severe disease. Here, we further analyzed data collected on enrolled CSSCD infants for the predictive value of those markers for stroke and death later in life. Three hundred fifty-four CSSCD subjects were identified who had absolute reticulocyte counts (ARC) measured during infancy (2 to 6 months of age). Infants with higher ARC had significantly increased risk of stroke or death during childhood; lower hemoglobin levels also increased the risk but to a lesser degree than ARC. WBC levels and dactylitis were not predictive of death or stroke. These data suggest that reticulocytosis among asymptomatic infants with sickle cell anemia is associated with an increased risk of death or stroke during childhood.

  15. Two-stage association study in Chinese Han identifies two independent associations in CCR1/CCR3 locus as candidate for Behçet's disease susceptibility.

    PubMed

    Hou, Shengping; Xiao, Xiang; Li, Fuzhen; Jiang, Zhengxuan; Kijlstra, Aize; Yang, Peizeng

    2012-12-01

    Previous GWAS studies from Turkey suggested a potential risk locus at CCR1/CCR3 for Behçet's disease. However, this locus did not reach the GWAS significance threshold and has not yet been examined in other ethnic populations. The current study aimed to explore whether this locus was associated with Behçet's disease in Chinese Han and the functional role of the identified variants. A two-stage association study was performed in 653 patients and 1,685 controls using the iPLEX system. Real-time PCR was performed to examine the expression level of CCR1 and CCR3 genes. Haplotype analysis was used to construct the haplotype block. Logistic regression analysis was applied to calculate the independence of multiple associations. Bonferroni correction was applied to account for multiple testing. First stage analysis showed that ten SNPs, located in 3'UTR, 5'UTR in CCR1 or 5'UTR in CCR3, were significantly associated with Behçet's disease (P(c) = 0.018 to 1.3 × 10(-3)). The associations of six SNPs within this locus are independent after control for the genetic effect of rs17282391 using logistic regression analysis. Haplotype analysis identified three associated haplotypes: H3 (GTGAC), H6 (CCATTA) and H9 (CGA) (P(c) = 0.04 to 7.79 × 10(-4)). Three SNPs rs13084057, rs13092160 and rs13075270 showed consistent association in replication and combining studies (replication P(c) = 5.31 × 10(-5) to 1.44 × 10(-5); combining P(c) = 2.76 × 10(-7) to 6.50 × 10(-8)). Interestingly, eQTLs database reveals that SNP rs13092160 is eQTLs SNP, suggesting that this SNP is likely to be functional SNP that directly affects gene expression. The expression of CCR1 and CCR3 was increased in individuals with the CT genotype of rs13092160 (P < 0.05). No significant difference was found for the mRNA level of CCR1 and CCR3 between Behçet's patients and controls. These findings strongly indicate CCR1/CCR3 as a novel locus underlying Behçet's disease.

  16. [Anemia: guidelines comparison].

    PubMed

    Del Vecchio, Lucia

    2009-01-01

    The development of recombinant human erythropoietin and its introduction into the market in the late 1980s has significantly improved the quality of life of patients with chronic kidney disease (CKD) and reduced the need for blood transfusions. Starting from a cautious target, a progressive increase in the recommended hemoglobin levels has been observed over the years, in parallel with an increase in the obtained levels. This trend has gone together with the publication of findings of observational studies showing a relationship between the increase in hemoglobin levels and a reduction in the mortality risk, with the conduction of clinical trials testing the effects of complete anemia correction, and with the compilation of guidelines on anemia control in CKD patients by scientific societies and organizations. In the last two years, evidence of a possible increase in the mortality risk in those patients who were randomized to high hemoglobin levels has resulted in a decrease in the upper limit of the recommended Hb target to be obtained with erythropoietin stimulating agents (ESA), and consequently in a narrowing of the target range. Comparison of guidelines on anemia control in CKD patients is an interesting starting point to discuss single recommendations, strengthen their importance, or suggest new topics of research to fill up important gaps in knowledge.

  17. Soluble transferrin receptor and transferrin receptor-ferritin index in iron deficiency anemia and anemia in rheumatoid arthritis.

    PubMed

    Margetic, Sandra; Topic, Elizabeta; Ruzic, Dragica Ferenec; Kvaternik, Marina

    2005-01-01

    The aim of the study was to evaluate the clinical efficiency of soluble transferrin receptor and transferrin receptor-ferritin index (sTfR/logF) in the diagnosis of iron deficiency anemia, as well as the differential diagnosis of iron deficiency anemia and anemia in rheumatoid arthritis. The study included 96 patients with anemia and 61 healthy volunteers as a control group. In healthy subjects there were no significant sex and age differences in the parameters tested. The study results showed these parameters to be reliable in the diagnosis of iron deficiency anemia, as well as in the differential diagnosis of iron deficiency anemia and anemia of chronic disease. The results indicate that sTfR/logF could be used to help differentiate coexisting iron deficiency in patients with anemia of chronic disease. Receiver operating characteristic analysis showed a higher discriminating power of transferrin receptor-ferritin index vs. soluble transferrin receptor in the diagnosis of iron deficiency anemia, as well as in the differential diagnosis between iron deficiency anemia and anemia of chronic disease. In patients with anemia in rheumatoid arthritis, the parameters tested showed no significant differences with respect to C-reactive protein concentration. These results suggested that the parameters tested are not affected by acute or chronic inflammatory disease.

  18. Quantitation of Marek's disease and chicken anemia viruses in organs of experimentally infected chickens and commercial chickens by multiplex real-time PCR.

    PubMed

    Davidson, Irit; Raibshtein, I; Al-Touri, A

    2013-06-01

    The worldwide distribution of chicken anemia virus (CAV) and Marek's disease virus (MDV) is well documented. In addition to their economic significance in single- or dual-virus infections, the two viruses can often accompany various other pathogens and affect poultry health either directly, by causing tumors, anemia, and delayed growth, or indirectly, by aggravating other diseases, as a result of their immunosuppressive effects. After a decade of employing the molecular diagnosis of those viruses, which replaced conventional virus isolation, we present the development of a real-time multiplex PCR for the simultaneous detection of both viruses. The real-time PCRs for MDV and for CAV alone are more sensitive than the respective end-point PCRs. In addition, the multiplex real-time shows a similar sensitivity when compared to the single real-time PCR for each virus. The newly developed real-time multiplex PCR is of importance in terms of the diagnosis and detection of low copies of each virus, MDV and CAV in single- and in multiple-virus infections, and its applicability will be further evaluated.

  19. Severe Aplastic Anemia Associated With Eosinophilic Fasciitis

    PubMed Central

    de Masson, Adèle; de Latour, Régis Peffault; Benhamou, Ygal; Moluçon-Chabrot, Cécile; Bay, Jacques-Olivier; Laquerrière, Annie; Picquenot, Jean-Michel; Michonneau, David; Leguy-Seguin, Vanessa; Rybojad, Michel; Bonnotte, Bernard; Jardin, Fabrice; Lévesque, Hervé; Bagot, Martine; Socié, Gérard

    2013-01-01

    Abstract Diffuse eosinophilic fasciitis (Shulman disease) is a rare sclerodermiform syndrome that, in most cases, resolves spontaneously or after corticosteroid therapy. It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. We report the cases of 4 patients with eosinophilic fasciitis and associated severe aplastic anemia. For 3 of these patients, aplastic anemia was refractory to conventional immunosuppressive therapy with antithymocyte globulin and cyclosporine. One of the patients received rituximab as a second-line therapy with significant efficacy for both the skin and hematologic symptoms. To our knowledge, this report is the first to describe rituximab used to treat eosinophilic fasciitis with associated aplastic anemia. In a literature review, we identified 19 additional cases of eosinophilic fasciitis and aplastic anemia. Compared to patients with isolated eosinophilic fasciitis, patients with eosinophilic fasciitis and associated aplastic anemia were more likely to be men (70%) and older (mean age, 56 yr; range, 18–71 yr). Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case. Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%). Only 5 patients (22%) achieved long-term remission (allogeneic hematopoietic stem cell transplantation: n = 2; cyclosporine-containing regimen: n = 2; high-dose corticosteroid-based regimen: n = 1). PMID:23429351

  20. [Anemia in patients with rheumatoid arthritis].

    PubMed

    Wahle, M

    2012-12-01

    One of the most frequent extra-articular organ manifestations in rheumatoid arthritis (RA) is anemia. As anemia in RA patients may result in severe symptoms and aggravation of other disease manifestations (e.g. arteriosclerosis), the influence on the course of RA is profound. However, the importance of anemia in RA patients is frequently underestimated. The etiology of anemia in RA is complex. Anemia of inflammation (AI) and iron deficiency anemia, alone or in combination are the most frequent forms of anemia in RA. Changes in iron metabolism are the leading causes of anemia in RA patients and mainly induced by the altered synthesis and function of hepcidin and ferroportin. Hepcidin, a peptide produced in the liver and immunocompetent cells, impairs the expression of ferroportin on iron-secreting cells, thus reducing iron bioavailability. The typical changes of iron metabolism and hepcidin synthesis in RA are induced by proinflammatory cytokines, primarily interleukin-6. Hence, the treatment of RA with cytokine antagonists has significant therapeutic implications on anemia in the context of inflammation and impaired iron metabolism.

  1. Anemias excluding cobalamin and folate deficiencies.

    PubMed

    Dublis, Stephanie; Shah, Shefali; Nand, Sucha; Anderes, Elise

    2014-01-01

    Anemias are one of the commonest maladies affecting humans. They result from either a failure of production by the bone marrow (hypoproliferative), or from premature destruction or loss (hyperproliferative) of red cells. Hypoproliferative anemias typically result from deficiencies of essential nutrients, stem cell abnormalities or deficiency, and infiltrative processes of the bone marrow. In the hyperproliferative forms, the bone marrow function is normal and anemia results from bleeding or shortened erythrocyte lifespan due to hemoglobinopathies, red cell enzyme disorders, membrane defects, or external factors such as antibodies, trauma, or heat injury. The etiology of anemia is frequently obvious, but when obscure, a systematic diagnostic approach frequently yields the answer. It is important to realize that anemias are usually a consequence of another disease process, which must be identified. Without correction of the underlying disease process, the treatment is likely to fail.

  2. A 21 Nucleotide Duplication on the α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease.

    PubMed

    Farashi, Samaneh; Faramarzi Garous, Negin; Zeinali, Fatemeh; Vakili, Shadi; Ashki, Mehri; Imanian, Hashem; Najmabadi, Hossein; Azarkeivan, Azita; Tamaddoni, Ahmad

    2015-01-01

    α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects in the α-globin gene cluster can result in α-thal that may develop into a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. Loss of one functional α gene, indicated as heterozygous α(+)-thal, shows minor hematological abnormalities. Homozygosity for α(+)- or heterozygosity for α(0)-thal have more severe hematological abnormalities due to a markedly reduced α chain output. At the molecular level, the absence of three α-globin genes resulting from the compound heterozygous state for α(0)- and α(+)-thal, lead to Hb H disease. Here we present a 21 nucleotide (nt) duplication consisting of six amino acids and 3 bp of intronic sequence at the exon-intron boundary, in both the α-globin genes, detected by direct DNA sequencing. This duplication was identified in three patients originating from two different Iranian ethnic groups and one Arab during more than 12 years. The clinical presentation of these individuals varies widely from a mild asymptomatic anemia (heterozygote in α1-globin gene) to a severely anemic state, diagnosed as an Hb H individual requiring blood transfusion (duplication on the α2-globin gene in combination with the - -(MED) double α-globin gene deletion). The third individual, who was homozygous for this nt duplication on the α1-globin gene, showed severe hypochromic microcytic anemia and splenomegaly. In the last decade, numerous α-globin mutations have demonstrated the necessity of prenatal diagnosis (PND) for α-thal, and this study has contributed another mutation as important enough that needs to be considered.

  3. Safety and Efficacy of PDpoetin for Management of Anemia in Patients with end Stage Renal Disease on Maintenance Hemodialysis: Results from a Phase IV Clinical Trial.

    PubMed

    Javidan, Abbas Norouzi; Shahbazian, Heshmatollah; Emami, Amirhossein; Yekaninejad, Mir Saeed; Emami-Razavi, Hassan; Farhadkhani, Masoumeh; Ahmadzadeh, Ahmad; Gorjipour, Fazel

    2014-08-26

    Recombinant human erythropoietin (rHuEPO) is available for correcting anemia. PDpoetin, a new brand of rHuEPO, has been certified by Food and Drug Department of Ministry of Health and Medical Education of Iran for clinical use in patients with chronic kidney disease. We conducted this post-marketing survey to further evaluate the safety and efficacy of PDpoetin for management of anemia in patients on maintenance hemodialysis. Patients from 4 centers in Iran were enrolled for this multicenter, open-label, uncontrolled phase IV clinical trial. Changes in blood chemistry, hemoglobin and hematocrit levels, renal function, and other characteristics of the patients were recorded for 4 months; 501 of the patients recruited, completed this study. Mean age of the patients was 50.9 (±16.2) years. 48.7% of patients were female. Mean of the hemoglobin value in all of the 4 centers was 9.29 (±1.43) g/dL at beginning of the study and reached 10.96 (±2.23) g/dL after 4 months and showed significant increase overall (P<0.001). PDpoetin dose was stable at 50-100 U/kg thrice weekly. Hemorheologic disturbancesand changes in blood electrolytes was not observed. No case of immunological reactions to PDpoetin was observed. Our study, therefore, showed that PDpoetin has significantly raised the level of hemoglobin in the hemodialysis patients (about 1.7±0.6 g/dL). Anemia were successfully corrected in 49% of patients under study. Use of this biosimilar was shown to be safe and effective for the maintenance of hemoglobin in patients on maintenance hemodialysis.

  4. Intravenous Versus Oral Iron for the Treatment of Anemia in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Bonovas, Stefanos; Fiorino, Gionata; Allocca, Mariangela; Lytras, Theodore; Tsantes, Argirios; Peyrin-Biroulet, Laurent; Danese, Silvio

    2016-01-01

    Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease (IBD). Our aim was to evaluate the comparative efficacy and harm of intravenous (IV) versus oral iron supplementation for correcting anemia in adult IBD patients.We conducted a systematic review and meta-analysis to integrate evidence from randomized controlled trials having enrolled adults with IBD, and comparing IV versus oral iron (head-to-head) for correcting iron-deficiency anemia. Medline, Embase, Scopus, and the Web of Science database were searched through July 2015. The Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, the ClinicalTrials.gov, and international conference proceedings were also investigated. Two reviewers independently abstracted study data and outcomes, and rated each trial's risk-of-bias. Pooled odds ratio (OR) estimates with their 95% CIs were calculated using fixed- and random-effects models.Five eligible studies, including 694 IBD patients, were identified. In meta-analysis, IV iron demonstrated a higher efficacy in achieving a hemoglobin rise of ≥2.0 g/dL as compared to oral iron (OR: 1.57, 95% CI: 1.13, 2.18). Treatment discontinuation rates, due to adverse events or intolerance, were lower in the IV iron groups (OR: 0.27, 95% CI: 0.13, 0.59). Similarly, the occurrence of gastrointestinal adverse events was consistently lower in the IV iron groups. On the contrary, serious adverse events (SAEs) were more frequently reported among patients receiving IV iron preparations (OR: 4.57, 95% CI: 1.11, 18.8); however, the majority of the reported SAEs were judged as unrelated or unlikely to be related to the study medication. We found no evidence of publication bias, or between-study heterogeneity, across all analyses. Risk of bias was high across primary studies, because patients and personnel were not blinded to the intervention.IV iron appears to be more effective and better tolerated than oral

  5. Development of mixed-type autoimmune hemolytic anemia and Evans' syndrome following chicken pox infection in a case of low-titer cold agglutinin disease.

    PubMed

    Tanaka, Yumi; Masuya, Masahiro; Katayama, Naoyuki; Miyata, Eri; Sugimoto, Yuka; Shibasaki, Tetsunori; Yamamura, Kentaro; Ohishi, Kohshi; Minami, Nobuyuki; Shiku, Hiroshi; Nobori, Tsutomu

    2006-10-01

    We describe a patient with low-titer cold agglutinin disease (CAD) who developed mixed-type autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenia following chicken pox infection. At least 1 year before admission to hospital, the patient had mild hemolytic anemia associated with low-titer cold agglutinins. A severe hemolytic crisis and thrombocytopenia (Evans' syndrome) occurred several days after infection with chicken pox, and the patient was referred to our hospital. Serological findings revealed the presence of both cold agglutinins and warm-reactive autoantibodies against erythrocytes, and the diagnosis was mixed-type AIHA. Following steroid therapy, the hemoglobin (Hb) level and platelet count improved. The patient was closely followed over a 10-year period with recurrent documented hemolysis after viral or bacterial infections. Warm-reactive autoantibodies have not been detected in the last 2 years, and only the immunoglobulin M anti-I cold agglutinins with a low titer and wide thermal amplitude have remained unchanged. Therefore, the patient has received at least 10 mg prednisolone daily to maintain a Hb level of 10 g/dL. To the best of our knowledge, no adult case of low-titer CAD that has evolved into mixed-type AIHA and Evans' syndrome after chicken pox infection has been previously reported in the literature.

  6. Cooley's Anemia: A Psychosocial Directory.

    ERIC Educational Resources Information Center

    National Center for Education in Maternal and Child Health, Washington, DC.

    The directory is intended to aid patients and their families who are coping with the genetic disorder of Cooley's anemia. A brief review of the disease covers background, genetics, symptoms, effect on the patient, treatment, and current research. The next section looks at psychosocial needs at various times (time of diagnosis, infancy and toddler…

  7. Acquired aplastic anemia in children.

    PubMed

    Hartung, Helge D; Olson, Timothy S; Bessler, Monica

    2013-12-01

    This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder.

  8. Investigation of nonpoikilocytic normochromic normocytic anemia.

    PubMed

    Ward, P C

    1979-03-01

    When the mean corpuscular volume is normal in an anemic patient, examination of a blood smear becomes of paramount importance. When the RBCs are normochronic, normocytic, and nonpoikilocytic, the reticulocyte count determines the line of investigation. When the count is increased, either hemorrhage or hemolysis is present. When the count is not increased (ie, normal or low), the differential diagnosis includes anemias due to iron deficiency, chronic disease, renal disease, hemodilution, marrow infiltration, and marrow failure (aplastic anemia). Some morphologic clues to cause other than those pertaining to RBC morphology are discussed and illustrated. A working approach to the investigation of nonpoikilocytic normochromic normocytic anemia is suggested.

  9. Identification of Genetic Loci Affecting the Severity of Symptoms of Hirschsprung Disease in Rats Carrying Ednrbsl Mutations by Quantitative Trait Locus Analysis

    PubMed Central

    Torigoe, Daisuke; Lei, Chuzhao; Lan, Xianyong; Chen, Hong; Sasaki, Nobuya; Wang, Jinxi; Agui, Takashi

    2015-01-01

    Hirschsprung’s disease (HSCR) is a congenital disease in neonates characterized by the absence of the enteric ganglia in a variable length of the distal colon. This disease results from multiple genetic interactions that modulate the ability of enteric neural crest cells to populate developing gut. We previously reported that three rat strains with different backgrounds (susceptible AGH-Ednrbsl/sl, resistant F344-Ednrbsl/sl, and LEH-Ednrbsl/sl) but the same null mutation of Ednrb show varying severity degrees of aganglionosis. This finding suggests that strain-specific genetic factors affect the severity of HSCR. Consistent with this finding, a quantitative trait locus (QTL) for the severity of HSCR on chromosome (Chr) 2 was identified using an F2 intercross between AGH and F344 strains. In the present study, we performed QTL analysis using an F2 intercross between the susceptible AGH and resistant LEH strains to identify the modifier/resistant loci for HSCR in Ednrb-deficient rats. A significant locus affecting the severity of HSCR was also detected within the Chr 2 region. These findings strongly suggest that a modifier gene of aganglionosis exists on Chr 2. In addition, two potentially causative SNPs (or mutations) were detected upstream of a known HSCR susceptibility gene, Gdnf. These SNPs were possibly responsible for the varied length of gut affected by aganglionosis. PMID:25790447

  10. Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2.

    PubMed Central

    San Millán, J L; Viribay, M; Peral, B; Martínez, I; Weissenbach, J; Moreno, F

    1995-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In approximately 86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of approximately 1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2. PMID:7825585

  11. Optimal management of pernicious anemia

    PubMed Central

    Andres, Emmanuel; Serraj, Khalid

    2012-01-01

    Pernicious anemia (also known as Biermer’s disease) is an autoimmune atrophic gastritis, predominantly of the fundus, and is responsible for a deficiency in vitamin B12 (cobalamin) due to its malabsorption. Its prevalence is 0.1% in the general population and 1.9% in subjects over the age of 60 years. Pernicious anemia represents 20%–50% of the causes of vitamin B12 deficiency in adults. Given its polymorphism and broad spectrum of clinical manifestations, pernicious anemia is a great pretender. Its diagnosis must therefore be evoked and considered in the presence of neurological and hematological manifestations of undetermined origin. Biologically, it is characterized by the presence of anti-intrinsic factor antibodies. Treatment is based on the administration of parenteral vitamin B12, although other routes of administration (eg, oral) are currently under study. In the present update, these various aspects are discussed with special emphasis on data of interest to the clinician. PMID:23028239

  12. Genetic diagnosis for congenital hemolytic anemia.

    PubMed

    Ohga, Shouichi

    Congenital hemolytic anemia is a group of monogenic diseases presenting with anemia due to increased destruction of circulating erythrocytes. The etiology of inherited anemia accounts for germline mutations of the responsible genes coding for the structural components of erythrocytes and extra-erythrocytes. The erythrocyte abnormalities are classified into three major disorders of red cell membrane defects, hemoglobinopathies, and red cell enzymopathies. The extra-erythrocyte abnormalities, typified by consumption coagulopathy and intravascular hemolysis, include Upshaw-Schulman syndrome and atypical hemolytic uremic syndrome. The clinical manifestations of congenital hemolytic anemia are anemia, jaundice, cholelithiasis and splenomegaly, while the onset mode and severity are both variable. Genetic overlapping of red cell membrane protein disorders, and distinct frequency and mutation spectra differing among races make it difficult to understand this disease entity. On the other hand, genetic modifiers for the phenotype of β-globin diseases provide useful information for selecting the optimal treatment and for long-term management. Recently, next generation sequencing techniques have enabled us to determine the novel causative genes in patients with undiagnosed hemolytic anemias. We herein review the concept and strategy for genetic diagnosis of inherited hemolytic anemias.

  13. Erythropoietic stress and anemia in diabetes mellitus.

    PubMed

    Singh, Dhruv K; Winocour, Peter; Farrington, Ken

    2009-04-01

    Anemia is one of the world's most common preventable conditions, yet it is often overlooked, especially in people with diabetes mellitus. Diabetes-related chronic hyperglycemia can lead to a hypoxic environment in the renal interstitium, which results in impaired production of erythropoietin by the peritubular fibroblasts and subsequent anemia. Anemia in patients with diabetes mellitus might contribute to the pathogenesis and progression of cardiovascular disease and aggravate diabetic nephropathy and retinopathy. Anemia occurs earlier in patients with diabetic renal disease than in nondiabetic individuals with chronic kidney disease. Although erythropoietin has been used to treat renal anemia for nearly two decades, debate persists over the optimal target hemoglobin level. Most guidelines recommend that hemoglobin levels be maintained between 105g/l and 125g/l. The suggested role of anemia correction--to prevent the progression of left ventricular hypertrophy in patients with diabetes mellitus--is yet to be established. However, an emphasis on regular screening for anemia, alongside that for other diabetes-related complications, might help to delay the progression of vascular complications in these patients.

  14. The Evidence-Based Evaluation of Iron Deficiency Anemia.

    PubMed

    Hempel, Eliana V; Bollard, Edward R

    2016-09-01

    Anemia is a prevalent disease with multiple possible etiologies and resultant complications. Iron deficiency anemia is a common cause of anemia and is typically due to insufficient intake, poor absorption, or overt or occult blood loss. Distinguishing iron deficiency from other causes of anemia is integral to initiating the appropriate treatment. In addition, identifying the underlying cause of iron deficiency is also necessary to help guide management of these patients. We review the key components to an evidence-based, cost-conscious evaluation of suspected iron deficiency anemia.

  15. Comparison of two recombinant erythropoietin formulations in patients with anemia due to end-stage renal disease on hemodialysis: A parallel, randomized, double blind study

    PubMed Central

    Pérez-Oliva, Jorge F; Casanova-González, Martha; García-García, Idrian; Porrero-Martín, Pedro J; Valenzuela-Silva, Carmen M; Hernández-Montero, Tairí; Lagarde-Ampudia, Marcia; Casanova-Kutsareva, Yuri; Ávila-Albuerne, Yisel; Vargas-Batista, Alicia; Bobillo-López, Hailen; Herrera-Valdés, Raúl; López-Saura, Pedro A

    2005-01-01

    Background Recombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia. A new EPO preparation was obtained in Cuba in order to make this treatment fully nationally available. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of two recombinant EPO formulations in patients with anemia due to end-stage renal disease on hemodialysis. Methods A parallel, randomized, double blind study was performed. A single 100 IU/Kg EPO dose was administered subcutaneously. Heberitro (Heber Biotec, Havana, formulation A), a newly developed product and Eprex (CILAG AG, Switzerland, formulation B), as reference treatment were compared. Thirty-four patients with anemia due to end-stage renal disease on hemodialysis were included. Patients had not received EPO previously. Serum EPO level was measured by enzyme immunoassay (EIA) during 120 hours after administration. Clinical and laboratory variables were determined as pharmacodynamic and safety criteria until 216 hours. Results Both groups of patients were similar regarding all demographic and baseline characteristics. EPO kinetics profiles were similar for both formulations; the pharmacokinetic parameters were very close (i.e., AUC: 4667 vs. 4918 mIU.h/mL; Cmax: 119.1 vs. 119.7 mIU/mL; Tmax: 13.9 vs. 18.1 h; half-life, 20.0 vs. 22.5 h for formulations A and B, respectively). The 90% confidence intervals for the ratio between both products regarding these metrics were close to the 0.8 – 1.25 range, considered necessary for bioequivalence. Differences did not reach 20% in any case and were not determined by a formulation effect, but probably by a patients' variability effect. Concerning pharmacodynamic features, a high similitude in reticulocyte counts increments until 216 hours and the percentage decrease in serum iron until 120 hours was observed. There were no differences between formulations regarding the adverse events and their intensity. The more

  16. Congenital spherocytic anemia

    MedlinePlus

    ... returns to normal. Possible Complications Complications may include: Gallstones Much lower red blood cell production (aplastic crisis) ... Elsevier Saunders; 2016:chap 14. Read More Anemia Gallstones Hemolytic anemia Review Date 2/1/2016 Updated ...

  17. [Common anemias in neonatology].

    PubMed

    Humbert, J; Wacker, P

    1999-01-28

    We describe the four most common groups of neonatal anemia and their treatments, with particular emphasis on erythropoietin therapy. The hemolytic anemias include the ABO incompatibility (much more frequent, nowadays, than the Rh incompatibility, which has nearly disappeared following the use of anti-D immunoglobulin in postpartum Rh-negative mothers), hereditary spherocytosis and G-6-PD deficiency. Among hypoplastic anemias, that caused by Parvovirus B19 predominates, by far, over Diamond-Blackfan anemia, alpha-thalassemia and the rare sideroblastic anemias. "Hemorrhagic" anemias occur during twin-to-twin transfusions, or during feto-maternal transfusions. Finally, the multifactorial anemia of prematurity develops principally as a result of the rapid expansion of the blood volume in this group of patients. Erythropoietin therapy, often at doses much higher than those used in the adult, should be seriously considered in most cases of non-hypoplastic neonatal anemias, to minimise maximally the use of transfusions.

  18. How Is Anemia Treated?

    MedlinePlus

    ... blood cells. Chelation (ke-LAY-shun) therapy for lead poisoning. Chelation therapy is used mainly in children. This ... iron-deficiency anemia are at increased risk of lead poisoning. Procedures If your anemia is severe, your doctor ...

  19. What Is Anemia?

    MedlinePlus

    ... Information for the Public » Health Topics » Anemia Explore Anemia What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related ...

  20. The Anemias of Athletes.

    ERIC Educational Resources Information Center

    Eichner, Edward R.

    1986-01-01

    Diagnosing anemia in athletes is complicated because athletes normally have a pseudoanemia that needs no treatment. Athletes, however, can develop anemia from iron deficiency or footstrike hemolysis, which require diagnosis and treatment. (Author/MT)

  1. Anemia in the Newborn

    MedlinePlus

    ... Cancer Caregivers Help Themselves Additional Content Medical News Anemia in the Newborn By Arthur E. Kopelman, MD, ... Prematurity (ROP) Necrotizing Enterocolitis (NEC) Jaundice in Newborns Anemia in the Newborn Polycythemia in the Newborn Thyroid ...

  2. The rs10757278 polymorphism of the 9p21.3 locus is associated with premature coronary artery disease in Polish patients.

    PubMed

    Niemiec, Pawel; Gorczynska-Kosiorz, Sylwia; Iwanicki, Tomasz; Krauze, Jolanta; Trautsolt, Wanda; Grzeszczak, Wladyslaw; Bochenek, Andrzej; Zak, Iwona

    2012-09-01

    Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25-55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19-3.66) as well as the G allele (OR=1.49, 95% CI: 1.08-2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population.

  3. The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

    PubMed Central

    Gorczynska-Kosiorz, Sylwia; Iwanicki, Tomasz; Krauze, Jolanta; Trautsolt, Wanda; Grzeszczak, Wladyslaw; Bochenek, Andrzej; Zak, Iwona

    2012-01-01

    Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25–55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19–3.66) as well as the G allele (OR=1.49, 95% CI: 1.08–2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population. PMID:22946666

  4. Anemia: progress in molecular mechanisms and therapies.

    PubMed

    Sankaran, Vijay G; Weiss, Mitchell J

    2015-03-01

    Anemia is a major source of morbidity and mortality worldwide. Here we review recent insights into how red blood cells (RBCs) are produced, the pathogenic mechanisms underlying various forms of anemia, and novel therapies derived from these findings. It is likely that these new insights, mainly arising from basic scientific studies, will contribute immensely to both the understanding of frequently debilitating forms of anemia and the ability to treat affected patients. Major worldwide diseases that are likely to benefit from new advances include the hemoglobinopathies (β-thalassemia and sickle cell disease); rare genetic disorders of RBC production; and anemias associated with chronic kidney disease, inflammation, and cancer. Promising new approaches to treatment include drugs that target recently defined pathways in RBC production, iron metabolism, and fetal globin-family gene expression, as well as gene therapies that use improved viral vectors and newly developed genome editing technologies.

  5. Myeloma and pernicious anemia.

    PubMed

    Perillie, P E

    1978-01-01

    Four cases of pernicious anemia developing in association with multiple myeloma are described. The description now of 14 cases demonstrating the association of these two disorders suggest a causative relationship. These observations, in addition to the previously well-documented increased coincidence of pernicious anemia and benign monoclonal gammopathy and pernicious anemia and hypoglobulinemia, suggest that screening for vitamine B12 deficiency in patients with gammopathies and for protein abnormalities in patients with pernicious anemia is indicated.

  6. A case of asymptomatic pancytopenia with clinical features of hemolysis as a presentation of pernicious anemia

    PubMed Central

    Kollipara, Venkateswara K.; Brine, Patrick L.; Gemmel, David; Ingnam, Sisham

    2016-01-01

    Pernicious anemia is an autoimmune disease with a variety of clinical presentations. We describe a case of pernicious anemia presenting with pancytopenia with hemolytic features. Further workup revealed very low vitamin B12 levels and elevated methylmalonic acid. It is important for a general internist to identify pernicious anemia as one of the cause of pancytopenia and hemolytic anemia to avoid extensive workup. Pernicious anemia can present strictly with hematological abnormalities without neurological problems or vice versa as in our case. PMID:27609735

  7. Management of Iron Deficiency Anemia

    PubMed Central

    Jimenez, Kristine; Kulnigg-Dabsch, Stefanie

    2015-01-01

    Anemia affects one-fourth of the world’s population, and iron deficiency is the predominant cause. Anemia is associated with chronic fatigue, impaired cognitive function, and diminished well-being. Patients with iron deficiency anemia of unknown etiology are frequently referred to a gastroenterologist because in the majority of cases the condition has a gastrointestinal origin. Proper management improves quality of life, alleviates the symptoms of iron deficiency, and reduces the need for blood transfusions. Treatment options include oral and intravenous iron therapy; however, the efficacy of oral iron is limited in certain gastrointestinal conditions, such as inflammatory bowel disease, celiac disease, and autoimmune gastritis. This article provides a critical summary of the diagnosis and treatment of iron deficiency anemia. In addition, it includes a management algorithm that can help the clinician determine which patients are in need of further gastrointestinal evaluation. This facilitates the identification and treatment of the underlying condition and avoids the unnecessary use of invasive methods and their associated risks. PMID:27099596

  8. Targeted gene therapy and cell reprogramming in Fanconi anemia

    PubMed Central

    Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A

    2014-01-01

    Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. PMID:24859981

  9. Advancements in anemias related to chronic conditions.

    PubMed

    Guidi, Gian Cesare; Lechi Santonastaso, Clara

    2010-09-01

    Anemia of chronic disease (ACD), the most frequent anemia among hospitalized patients, occurs in chronic inflammatory disorders, such as chronic infections, cancer and autoimmune diseases. Different causes contribute to ACD including diversion of iron traffic, diminished erythropoiesis, blunted response to erythropoietin, erythrophagocytosis, hematologic malignancies and solid tumors. A particular case of ACD is represented by anemia of chronic kidney disease (CKD). ACD is characterized by hyposideremia and altered iron transport. Cytokines are implicated in the ACD by reducing erythropoiesis and increasing iron sequestration in the reticuloendothelial system. The regulation of iron absorption across the epithelium of the proximal small intestine is essential for maintaining body iron concentrations within a physiologically defined range. Hepcidin controls cellular iron efflux by binding to the iron export protein ferroportin, causing ferroportin to be phosphorylated and degraded in lysosomes. Finally, hepcidin inhibits iron release from the reticulo-endothelial system. Increased expression of hepcidin leads to decreased iron absorption and iron deficient anemia. Hepcidin, therefore, is a negative regulator of iron transport in plasma. Causes of anemia in patients with CKD are multifactorial, but the most well-known cause is inadequate erythropoietin production. In these patients, anemia increases the risk of either cardiovascular disease or renal failure.

  10. Role of Complement in Autoimmune Hemolytic Anemia

    PubMed Central

    Berentsen, Sigbjørn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed. PMID:26696798

  11. Role of Complement in Autoimmune Hemolytic Anemia.

    PubMed

    Berentsen, Sigbjørn

    2015-09-01

    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  12. Anemia of immobility: caused by adipocyte accumulation in bone marrow.

    PubMed

    Payne, Michael W C; Uhthoff, Hans K; Trudel, Guy

    2007-01-01

    Anemia of chronic disease has long been used to classify a non-regenerative, low-grade, chronic, normocytic, normochromic anemia that presents with no obvious etiology. Within this group, some patients have a chronic inflammatory condition that limits erythrocyte generation or access to iron stores. This specific type of anemia has been termed anemia of chronic inflammation. However, a substantial remainder of patients diagnosed with anemia of chronic disease present with no active inflammation. These include many clinical populations with reduced limb loading, such as spinal cord injured patients, astronauts, elderly people with limited mobility and experimental bed-rest subjects. In some populations with decreased mobility, accumulation of fat in the bone marrow has been demonstrated. We hypothesize that adipocyte accumulation in bone marrow both passively and actively impairs erythropoiesis and thus defines a new type of anemia called anemia of immobility. The non-specific umbrella term anemia of chronic disease thus becomes obsolete in favour of either the diagnosis of anemia of immobility or anemia of chronic inflammation according to the distinct mechanism involved.

  13. Somatic variation plays a key role in the evolution of the Vf gene family residing in the Vf locus that confers resistance to apple scab disease.

    PubMed

    Xu, Mingliang; Korban, Schuyler S

    2004-07-01

    A cluster of four receptor-like genes has been previously identified in the Vf locus of the crabapple Malus floribunda clone 821 that confers resistance to five races of the fungal pathogen Venturia inaequalis, the casual agent of apple scab disease. Pairwise comparisons of the four Vf paralogs in both promoter and coding regions reveal their timeline evolutionary history. The four Vf paralogs have evolved from four ancient Vf members resulting from two sequential duplication events of a single Vf progenitor initially present in the Malus genome. The coding sequences of the four Vf paralogs are characterized with high numbers of unique polymorphic nucleotides, a number of short duplications/deletions, various deletions of complete LRR copy units, and a casual insert of a transposon-like element. Significant high ratios of nonsynonymous to synonymous substitutions, Ka/Ks, are observed in the putative ligand binding residues in the LRR domains. No sequence exchange between the four Vf paralogs is observed. Compared with promoter regions, only nucleotide substitutions are dramatically elevated in the coding regions. The results presented in this study strongly indicate that the Vf locus is under strong and steady horizontal selective pressures imposed by the fungal pathogen V. inaequalis, and divergent selection on somatic variations plays a key role in shaping the resistance specificity.

  14. Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4C locus SH3TC2.

    PubMed

    Brewer, Megan Hwa; Ma, Ki Hwan; Beecham, Gary W; Gopinath, Chetna; Baas, Frank; Choi, Byung-Ok; Reilly, Mary M; Shy, Michael E; Züchner, Stephan; Svaren, John; Antonellis, Anthony

    2014-10-01

    Loss-of-function mutations in the Src homology 3 (SH3) domain and tetratricopeptide repeats 2 (SH3TC2) gene cause autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy. The SH3TC2 protein has been implicated in promyelination signaling through axonal neuregulin-1 and the ERBB2 Schwann cell receptor. However, little is known about the transcriptional regulation of the SH3TC2 gene. We performed computational and functional analyses that revealed two cis-acting regulatory elements at SH3TC2-one at the promoter and one ∼150 kb downstream of the transcription start site. Both elements direct reporter gene expression in Schwann cells and are responsive to the transcription factor SOX10, which is essential for peripheral nervous system myelination. The downstream enhancer harbors a single-nucleotide polymorphism (SNP) that causes an ∼80% reduction in enhancer activity. The SNP resides directly within a predicted binding site for the transcription factor cAMP response element binding protein (CREB), and we demonstrate that this regulatory element binds to CREB and is activated by CREB expression. Finally, forskolin induces Sh3tc2 expression in rat primary Schwann cells, indicating that SH3TC2 is a CREB target gene. These findings prompted us to determine if SNP genotypes at SH3TC2 are associated with differential phenotypes in the most common demyelinating peripheral neuropathy, CMT1A. Interestingly, this revealed several associations between SNP alleles and disease severity. In summary, our data indicate that SH3TC2 is regulated by the transcription factors CREB and SOX10, define a regulatory SNP at this disease-associated locus and reveal SH3TC2 as a candidate modifier locus of CMT disease phenotypes.

  15. Unexpected Anemia and Reticulocytopenia in an Adolescent With Sickle Cell Anemia Receiving Chronic Transfusion Therapy.

    PubMed

    Blauel, Emily R; Grossmann, Lily T; Vissa, Madhav; Miller, Scott T

    2015-10-01

    In a patient with sickle cell disease receiving chronic transfusion, exacerbation of anemia with reticulocytopenia must prompt consideration of a delayed hemolytic transfusion reaction with hyperhemolysis, as further transfusion may worsen this condition; definitive diagnosis is sometimes difficult. Anemia evolving during parvovirus B19-induced erythroid hypoplasia (transient aplastic crisis) should be attenuated in chronic transfusion patients due to superior survival of transfused over endogenous red blood cells. A 16-year-old with sickle cell disease receiving chronic transfusion of modified intensity (goal to maintain hemoglobin S<50%) who developed symptomatic anemia with reticulocytopenia was later shown to have had transient aplastic crisis.

  16. Fanconi's Anemia Effect or Sickle Cell Anemia Effect: That is the Question.

    PubMed

    Unal, Sule; Chui, David H K; Gumruk, Fatma

    2015-01-01

    A 16-year-old boy who was diagnosed to have sickle cell anemia was referred to our center. The parental consanguinity, growth retardation and dysmorphic features prompted a search for possible Fanconi's Anemia (FA). The diepoxybutane (DEB) test was positive, confirming FA. The interaction of both diseases might account for his relatively mild phenotype in terms of both sickle cell anemia (or Hb S, HBB: c.20A > T) and FA. The high Hb F level that might be related to concomitant FA, may have caused a milder phenotype of sickle cell anemia, whereas nitric oxide (NO) depletion as a consequence of sickle cell anemia, may have caused a delay in the bone marrow failure of FA.

  17. Ferric Maltol Is Effective in Correcting Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease: Results from a Phase-3 Clinical Trial Program

    PubMed Central

    Ahmad, Tariq; Tulassay, Zsolt; Baumgart, Daniel C.; Bokemeyer, Bernd; Büning, Carsten; Howaldt, Stefanie; Stallmach, Andreas

    2014-01-01

    Background: Iron deficiency anemia (IDA) is frequently seen in inflammatory bowel disease. Traditionally, oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease exacerbation. This multicenter phase-3 study tested the efficacy and safety of ferric maltol, a complex of ferric (Fe3+) iron with maltol (3-hydroxy-2-methyl-4-pyrone), as a novel oral iron therapy for IDA. Methods: Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn's disease, mild-to-moderate IDA (9.5–12.0 g/dL and 9.5–13.0 g/dL in females and males, respectively), and documented failure on previous oral ferrous products received oral ferric maltol capsules (30 mg twice a day) or identical placebo for 12 weeks according to a randomized, double-blind, placebo-controlled study design. The primary efficacy endpoint was change in hemoglobin (Hb) from baseline to week 12. Safety and tolerability were assessed. Results: Of 329 patients screened, 128 received randomized therapy (64 ferric maltol-treated and 64 placebo-treated patients) and comprised the intent-to-treat efficacy analysis: 55 ferric maltol patients (86%) and 53 placebo patients (83%) completed the trial. Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4, 8, and 12: mean (SE) 1.04 (0.11) g/dL, 1.76 (0.15) g/dL, and 2.25 (0.19) g/dL, respectively (P < 0.0001 at all time-points; analysis of covariance). Hb was normalized in two-thirds of patients by week 12. The safety profile of ferric maltol was comparable with placebo, with no impact on inflammatory bowel disease severity. Conclusions: Ferric maltol provided rapid clinically meaningful improvements in Hb and showed a favorable safety profile, suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease. PMID:25545376

  18. Aplastic anemia

    MedlinePlus

    ... sister. This is called a matched sibling donor. Older people and those who do not have a matched sibling donor are given medicine to suppress the immune system. These medicines may allow the bone marrow to once again make healthy blood cells. But the disease may return ( ...

  19. Relationships between systemic vascular resistance, blood rheology and nitric oxide in children with sickle cell anemia or sickle cell-hemoglobin C disease.

    PubMed

    Lamarre, Yann; Hardy-Dessources, Marie-Dominique; Romana, Marc; Lalanne-Mistrih, Marie-Laure; Waltz, Xavier; Petras, Marie; Doumdo, Lydia; Blanchet-Deverly, Anne; Martino, Jean; Tressières, Benoît; Maillard, Frederic; Tarer, Vanessa; Etienne-Julan, Maryse; Connes, Philippe

    2014-01-01

    Vascular function has been found to be impaired in patients with sickle cell disease (SCD). The present study investigated the determinants of systemic vascular resistance in two main SCD syndromes in children: sickle cell anemia (SCA) and sickle cell-hemoglobin C disease (SCC). Nitric oxide metabolites (NOx), hematological, hemorheological, and hemodynamical parameters were investigated in 61 children with SCA and 49 children with SCC. While mean arterial pressure was not different between SCA and SCC children, systemic vascular resistance (SVR) was greater in SCC children. Although SVR and blood viscosity (ηb) were not correlated in SCC children, the increase of ηb (+18%) in SCC children compared to SCA children results in a greater mean SVR in this former group. SVR was positively correlated with ηb, hemoglobin (Hb) level and RBC deformability, and negatively with NOx level in SCA children. Multivariate linear regression model showed that both NOx and Hb levels were independently associated with SVR in SCA children. In SCC children, only NOx level was associated with SVR. In conclusion, vascular function of SCC children seems to better cope with higher ηb compared to SCA children. Since the occurrence of vaso-occlusive like complications are less frequent in SCC than in SCA children, this finding suggests a pathophysiological link between the vascular function alteration and these clinical manifestations. In addition, our results suggested that nitric oxide metabolism plays a key role in the regulation of SVR, both in SCA and SCC.

  20. The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1)

    SciTech Connect

    Tsugu, H.; Horowitz, R.; Gibson, N.

    1994-12-01

    Sera from approximately 30% of patients with systemic lupus erythematosus (SLE) contain high titers of autoantibodies that bind to the 52-kDa Ro/SSA protein. We previously detected polymorphisms in the 52-kDa Ro/SSA gene (SSA1) with restriction enzymes, one of which is strongly associated with the presence of SLE (P < 0.0005) in African Americans. A higher disease frequency and more severe forms of the disease are commonly noted among these female patients. To determine the location and nature of this polymorphism, we obtained two clones that span 8.5 kb of the 52-kDa Ro/SSA locus including its upstream regulatory region. Six exons were identified, and their nucleotide sequences plus adjacent noncoding regions were determined. No differences were found between these exons and the coding region of one of the reported cDNAs. The disease-associated polymorphic site suggested by a restriction enzyme map and confirmed by DNA amplification and nucleotide sequencing was present upstream of exon 1. This polymorphism may be a genetic marker for a disease-related variation in the coding region for the protein or in the upstream regulatory region of this gene. Although this RFLP is present in Japanese, it is not associated with lupus in this race. 41 refs., 4 figs., 2 tabs.

  1. Anemia, fatigue and aging.

    PubMed

    Balducci, L

    2010-12-01

    Aging is associated with increased incidence and prevalence of both cancer and anemia. Cancer and aging may conspire in making anemia more frequent and more severe. This article reviews the causes and the consequences of anemia in the older individual. The most common causes include chronic inflammation that is a typical manifestation of aging, iron deficiency that may be due to chronic hemorrhage, malabsorption and Helicobacter pylori infection, cobalamin deficiency from malabsorption and renal insufficiency. Other causes of anemia whose prevalence is not well established include myelodysplasia, copper deficiency, hypothyroidism, and sarcopenia. Anemia is associated with increased risk of mortality, functional dependence, dementia, falls, and chemotherapy-related toxicity. When correcting the anemia of older cancer patients one should remember that the erythropoietic stimulating agents (ESA) may stimulate cancer growth and cause thrombosis. These products may be safe when given exclusively to patients receiving chemotherapy and when the hemoglobin levels are maintained below 12 g/dL.

  2. Musculoskeletal manifestations of chronic anemias.

    PubMed

    Martinoli, Carlo; Bacigalupo, Lorenzo; Forni, Gian Luca; Balocco, Manuela; Garlaschi, Giacomo; Tagliafico, Alberto

    2011-07-01

    This article provides an overview of the current use of diagnostic imaging modalities in the evaluation of a heterogeneous group of disorders causing chronic anemias by impaired blood cell production (inherited bone marrow failure syndromes of childhood, aplastic anemia and myelodysplastic syndromes, β-thalassemia) or increased blood cell destruction (sickle cell disease). During the course of these disorders, various musculoskeletal abnormalities can be encountered, including marrow hyperplasia, reversion of yellow marrow to red marrow, growth disturbances, and, occasionally, extramedullary hematopoiesis. Diagnostic imaging may help the clinician to identify specific complications related to either the disease (e.g., bone infarction and acute osteomyelitis in sickle cell disease) or transfusion (e.g., iron overload due to increased hemolysis) and iron chelation (e.g., desferrioxamine-related dysplastic bone changes and deferiprone-related degenerative arthritis) treatments. In this field, magnetic resonance imaging plays a pivotal role because of its high tissue contrast that enables early assessment of bone marrow changes before they become apparent on plain films or computed tomography or metabolic changes occur on bone scintigraphy or positron emission tomography scan. Overall, familiarity with the range of radiological appearances in chronic anemias is important to diagnose complications and establish appropriate therapy.

  3. How Is Pernicious Anemia Treated?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Pernicious Anemia Treated? Doctors treat pernicious anemia by replacing the missing vitamin B12 in the body. People who have pernicious anemia may need lifelong treatment. The goals of treating ...

  4. How Is Aplastic Anemia Treated?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Aplastic Anemia Treated? Treatments for aplastic anemia include blood transfusions , blood and marrow stem cell ... a transplant. Removing a known cause of aplastic anemia, such as exposure to a toxin, also may ...

  5. Inborn anemias in mice

    SciTech Connect

    Bernstein, S.E.; Barker, J.E.; Russell, E.S.

    1981-06-01

    hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, five hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values, (b) determinations of radiosensitivity under a variety of conditions, (c) measurements of iron metabolism and heme synthesis, (d) histological and biochemical study of blood-forming tissue, (e) functional tests of the stem cell component, (f) examination of responses to erythroid stimuli, and (g) transplantation of tissue between individuals of differently affected genotypes.

  6. Anemia in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Barbieri, Jéssica; Fontela, Paula Caitano; Winkelmann, Eliane Roseli; Zimmermann, Carine Eloise Prestes; Sandri, Yana Picinin; Mallet, Emanelle Kerber Viera; Frizzo, Matias Nunes

    2015-01-01

    The objective of this study was to evaluate the prevalence of anemia in DM2 patients and its correlation with demographic and lifestyle and laboratory variables. This is a descriptive and analytical study of the type of case studies in the urban area of the Ijuí city, registered in programs of the Family Health Strategy, with a total sample of 146 patients with DM2. A semistructured questionnaire with sociodemographic and clinical variables and performed biochemical test was applied. Of the DM2 patients studied, 50 patients had anemia, and it was found that the body mass items and hypertension and hematological variables are significantly associated with anemia of chronic disease. So, the prevalence of anemia is high in patients with DM2. The set of observed changes characterizes the anemia of chronic disease, which affects quality of life of diabetic patients and is associated with disease progression, development, and comorbidities that contribute significantly to increasing the risk of cardiovascular diseases.

  7. Genomic and Epigenetic Complexity of the FOXF1 Locus in 16q24.1: Implications for Development and Disease.

    PubMed

    Dharmadhikari, Avinash V; Szafranski, Przemyslaw; Kalinichenko, Vladimir V; Stankiewicz, Pawel

    2015-04-01

    The FOXF1 (Forkhead box F1) gene, located on chromosome 16q24.1 encodes a member of the FOX family of transcription factors characterized by a distinct forkhead DNA binding domain. FOXF1 plays an important role in epithelium-mesenchyme signaling, as a downstream target of Sonic hedgehog pathway. Heterozygous point mutations and genomic deletions involving FOXF1 have been reported in newborns with a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV). In addition, genomic deletions upstream to FOXF1 identified in ACDMPV patients have revealed that FOXF1 expression is tightly regulated by distal tissue-specific enhancers. Interestingly, FOXF1 has been found to be incompletely paternally imprinted in human lungs; characterized genomic deletions arose de novo exclusively on maternal chromosome 16, with most of them being Alu-Alu mediated. Regulation of FOXF1 expression likely utilizes a combination of chromosomal looping, differential methylation of an upstream CpG island overlapping GLI transcription factor binding sites, and the function of lung-specific long non-coding RNAs (lncRNAs). FOXF1 knock-out mouse models demonstrated its critical role in mesoderm differentiation and in the development of pulmonary vasculature. Additionally, epigenetic inactivation of FOXF1 has been reported in breast and colorectal cancers, whereas overexpression of FOXF1 has been associated with a number of other human cancers, e.g. medulloblastoma and rhabdomyosarcoma. Constitutional duplications of FOXF1 have recently been reported in congenital intestinal malformations. Thus, understanding the genomic and epigenetic complexity at the FOXF1 locus will improve diagnosis, prognosis, and treatment of ACDMPV and other human disorders associated with FOXF1 alterations.

  8. Genomic and Epigenetic Complexity of the FOXF1 Locus in 16q24.1: Implications for Development and Disease

    PubMed Central

    Dharmadhikari, Avinash V.; Szafranski, Przemyslaw; Kalinichenko, Vladimir V.; Stankiewicz, Pawel

    2015-01-01

    The FOXF1 (Forkhead box F1) gene, located on chromosome 16q24.1 encodes a member of the FOX family of transcription factors characterized by a distinct forkhead DNA binding domain. FOXF1 plays an important role in epithelium-mesenchyme signaling, as a downstream target of Sonic hedgehog pathway. Heterozygous point mutations and genomic deletions involving FOXF1 have been reported in newborns with a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV). In addition, genomic deletions upstream to FOXF1 identified in ACDMPV patients have revealed that FOXF1 expression is tightly regulated by distal tissue-specific enhancers. Interestingly, FOXF1 has been found to be incompletely paternally imprinted in human lungs; characterized genomic deletions arose de novo exclusively on maternal chromosome 16, with most of them being Alu-Alu mediated. Regulation of FOXF1 expression likely utilizes a combination of chromosomal looping, differential methylation of an upstream CpG island overlapping GLI transcription factor binding sites, and the function of lung-specific long non-coding RNAs (lncRNAs). FOXF1 knock-out mouse models demonstrated its critical role in mesoderm differentiation and in the development of pulmonary vasculature. Additionally, epigenetic inactivation of FOXF1 has been reported in breast and colorectal cancers, whereas overexpression of FOXF1 has been associated with a number of other human cancers, e.g. medulloblastoma and rhabdomyosarcoma. Constitutional duplications of FOXF1 have recently been reported in congenital intestinal malformations. Thus, understanding the genomic and epigenetic complexity at the FOXF1 locus will improve diagnosis, prognosis, and treatment of ACDMPV and other human disorders associated with FOXF1 alterations. PMID:26085809

  9. H.pylori associated with iron deficiency anemia even in celiac disease patients; strongly evidence based but weakly reflected in practice

    PubMed Central

    Rostami-Nejad, Mohammad; Aldulaimi, David; Livett, Helen; Rostami, Kamran

    2015-01-01

    Inflammation can lead to malabsorption of important micronutrients such as iron. Malabsorption and nutritional deficiency can be caused by a variety of pathological and environmental factors causing a range of other symptoms commonly caused by both H. pylori infection and coeliac disease (CD). National guidelines suggest the routine taking of duodenal biopsies to exclude CD when investigating patients for iron deficiency anemia (IDA). Studies suggest that in absence of positive antibodies, IDA is rarely caused by CD. Recent British Society of Gastroenterology guidelines discourage the routine duodenal biopsies in low risk cases but despite this guidance, taking duodenal biopsies for IDA is a common practice. Many studies have reported that H. pylori infection is associated with IDA even in patients with CD. In countries with low H. pylori prevalence we still detect more H. pylori than CD standing behind IDA. Despite the strong association between IDA and H. pylori, taking biopsies to diagnose H. pylori infection is not usually a routine part of the diagnostic workup to identify the etiology of IDA. In this review we will discuss the impact of H. pylori in IDA and highlight the possible gaps in identifying the IDA etiology. PMID:26328039

  10. Characteristics of anemia in subclinical and overt hypothyroid patients.

    PubMed

    Erdogan, Mehmet; Mehmet, Erdogan; Kösenli, Aybike; Aybike, Kosenli; Ganidagli, Sencer; Kulaksizoglu, Mustafa; Mustafa, Kulaksizoglu

    2012-01-01

    Thyroid hormones stimulate directly or indirectly growth of erythroid colonies through erythropoietin. Anemia is often the first sign of hypothyroidism. Hypothyroidism can cause a wide variety of anemic disorders. Numerous mechanisms are involved in the pathogenesis of these anemias that can be microcytic, macrocytic and normocytic. We designed this study to investigate the anemia frequency and if present, etiology of anemia in hypothyroid patients. 100 patients with overt hypothyroid, 100 patients with subclinical hypothyroid, and 200 healthy controls were enrolled in this study. Overt hypothyroidism diagnosis is done when elevated TSH and low levels of free T4 and/or free T3 have been observed. Subclinical hypothyroidism is defined as elevated serum TSH with normal free T(4) and free T(3) levels. Peripheral smears of the anemic patients were examined. Anemia prevalence was 43% in the overt hypothyroid group, 39% in the subclinical hypothyroid group, and 26% in the control group (p=0.0003 and p=0.021 respectively related to controls). Thus, the frequency of anemia in subclinical hypothyroidism is as high as that in overt hypothyroidism. There was no difference between the hypothyroid groups in terms of anemia. Vitamin B12, Fe, and folic acid were similar between these groups. According to our findings, anemia of chronic disease is the most common type of anemia in hypothyroid patients. Suspicion of hypothyroidism should be considered in anemias with uncertain etiology.

  11. Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

    PubMed

    Daulatzai, Mak Adam

    2016-10-01

    Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

  12. Bed bugs reproductive life cycle in the clothes of a patient suffering from Alzheimer’s disease results in iron deficiency anemia

    PubMed Central

    Sabou, Marcela; Gallo Imperiale, Delphine; Andrès, Emmanuel; Abou-Bacar, Ahmed; Foeglé, Jacinthe; Lavigne, Thierry; Kaltenbach, Georges; Candolfi, Ermanno

    2013-01-01

    We report the case of an 82-year-old patient, hospitalized for malaise. Her clothes were infested by numerous insects and the entomological analysis identified them as being Cimex lectularius (bed bugs). The history of the patient highlighted severe cognitive impairment. The biological assessment initially showed a profound microcytic, aregenerative, iron deficiency anemia. A vitamin B12 deficiency due to pernicious anemia (positive intrinsic factor antibodies) was also highlighted, but this was not enough to explain the anemia without macrocytosis. Laboratory tests, endoscopy and a CT scan eliminated a tumor etiology responsible for occult bleeding. The patient had a mild itchy rash which was linked to the massive colonization by the bed bugs. The C. lectularius bite is most often considered benign because it is not a vector of infectious agents. Far from trivial, a massive human colonization by bed bugs may cause such a hematic depletion that severe microcytic anemia may result. PMID:23673315

  13. Fifth Cooley's anemia symposium

    SciTech Connect

    Bank, A.; Anderson, W.F.; Zaino, E.C.

    1985-01-01

    This book discusses the topics presented at the symposium on the subject of 'Thalassemia'. Sickle cell anemia is also briefly discussed. The aspects discussed are chromosomal defects of anemias particularly globin synthesis, and the role of messenger RNA and other chromosomes.

  14. The I2C family from the wilt disease resistance locus I2 belongs to the nucleotide binding, leucine-rich repeat superfamily of plant resistance genes.

    PubMed Central

    Ori, N; Eshed, Y; Paran, I; Presting, G; Aviv, D; Tanksley, S; Zamir, D; Fluhr, R

    1997-01-01

    Characterization of plant resistance genes is an important step in understanding plant defense mechanisms. Fusarium oxysporum f sp lycopersici is the causal agent of a vascular wilt disease in tomato. Genes conferring resistance to plant vascular diseases have yet to be described molecularly. Members of a new multigene family, complex I2C, were isolated by map-based cloning from the I2 F. o. lycopersici race 2 resistance locus. The genes show structural similarity to the group of recently isolated resistance genes that contain a nucleotide binding motif and leucine-rich repeats. Importantly, the presence of I2C antisense transgenes abrogated race 2 but not race 1 resistance in otherwise normal plants. Expression of the complete sense I2C-1 transgene conferred significant but partial resistance to F. o. lycopersici race 2. All members of the I2C gene family have been mapped genetically and are dispersed on three different chromosomes. Some of the I2C members cosegregate with other tomato resistance loci. Comparison within the leucine-rich repeat region of I2C gene family members shows that they differ from each other mainly by insertions or deletions. PMID:9144960

  15. Targeted Gene Addition to a Safe Harbor locus in human CD34+ Hematopoietic Stem Cells for Correction of X-linked Chronic Granulomatous Disease

    PubMed Central

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H.; Chan, Andy; Pearl, Jocelynn R.; Paschon, David E.; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A.; Zarember, Kol A.; Peshwa, Madhusudan V.; Gregory, Philip D.; Urnov, Fyodor D.; Malech, Harry L.

    2016-01-01

    Gene therapy with genetically modified human CD34+ hematopoietic stem cells (HSCs) may be safer using targeted integration (TI) of transgenes into a genomic ‘safe harbor’ site than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno associated virus (AAV) 6 delivery of donor constructs in human HSCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus-positive HSCs with 6–16% human cell marking were observed following engraftment into mice. In HSCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 in resulted in ~15% gp91phox expression and increased NADPH oxidase activity in ex vivo–derived neutrophils. In mice transplanted with corrected HSCs, 4–11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. PMID:26950749

  16. Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson's Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra

    PubMed Central

    Corradini, Beatriz Raposo; Tampellini, Edilaine; Farfel, José Marcelo; Grinberg, Lea Tenenholz; Moreira-Filho, Carlos Alberto

    2014-01-01

    Parkinson's disease (PD)—classically characterized by severe loss of dopaminergic neurons in the substantia nigra pars compacta—has a caudal-rostral progression, beginning in the dorsal motor vagal nucleus and, in a less extent, in the olfactory system, progressing to the midbrain and eventually to the basal forebrain and the neocortex. About 90% of the cases are idiopathic. To study the molecular mechanisms involved in idiopathic PD we conducted a comparative study of transcriptional interaction networks in the dorsal motor vagal nucleus (VA), locus coeruleus (LC), and substantia nigra (SN) of idiopathic PD in Braak stages 4-5 (PD) and disease-free controls (CT) using postmortem samples. Gene coexpression networks (GCNs) for each brain region (patients and controls) were obtained to identify highly connected relevant genes (hubs) and densely interconnected gene sets (modules). GCN analyses showed differences in topology and module composition between CT and PD networks for each anatomic region. In CT networks, VA, LC, and SN hub modules are predominantly associated with neuroprotection and homeostasis in the ageing brain, whereas in the patient's group, for the three brain regions, hub modules are mostly related to stress response and neuron survival/degeneration mechanisms. PMID:25525598

  17. Mitochondrial iron metabolism and sideroblastic anemia.

    PubMed

    Sheftel, Alex D; Richardson, Des R; Prchal, Josef; Ponka, Prem

    2009-01-01

    Sideroblastic anemias are a heterogeneous group of disorders, characterized by mitochondrial iron overload in developing red blood cells. The unifying characteristic of all sideroblastic anemias is the ring sideroblast, which is a pathological erythroid precursor containing excessive deposits of non-heme iron in mitochondria with perinuclear distribution creating a ring appearance. Sideroblastic anemias may be hereditary or acquired. Hereditary sideroblastic anemias are caused by defects in genes present on the X chromosome (mutations in the ALAS2, ABCB7, or GRLX5 gene), genes on autosomal chromosomes, or mitochondrial genes. Acquired sideroblastic anemias are either primary (refractory anemia with ring sideroblasts, RARS, representing one subtype of the myelodysplastic syndrome) or secondary due to some drugs, toxins, copper deficiency, or chronic neoplastic disease. The pathogenesis of mitochondrial iron loading in developing erythroblasts is diverse. Ring sideroblasts can develop as a result of a heme synthesis defect in erythroblasts (ALAS2 mutations), a defect in iron-sulfur cluster assembly, iron-sulfur protein precursor release from mitochondria (ABCB7 mutations), or by a defect in intracellular iron metabolism in erythroid cells (e.g. RARS).

  18. [Hemolytic anemias in adults].

    PubMed

    Müller, A; Zimmermann, R; Krause, S W

    2011-11-01

    The erythrocyte lifespan in haemolytic anemia is shortened while erythropoesis is increased. Important labaratory findings are increased reticulocytes, LDH, indirect bilirubin and a decreased haptoglobin level. The most important diagnostic tool for further work up of hemolytic anemia is the direct antiglobulin test (DAT, Coombs test) to differentiate autoimmune hemolytic anemia (AIHA) from other causes. Another important group are fragmentation syndroms (hemolytic uremic syndrome and thrombotic thrombocytopenic purpura). In these forms of haemolytic anemia fragmented red blood cells can be found in the blood smear together with thrombocytopenia. A severe problem in paroxysmal nocturnal hematuria is the incidence of thrombosis. The following review describes the most important forms of hemolytic anemia in the adult and the diagnostic and therapeutic strategies.

  19. Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia.

    PubMed

    Bolar, Nikhita Ajit; Golzio, Christelle; Živná, Martina; Hayot, Gaëlle; Van Hemelrijk, Christine; Schepers, Dorien; Vandeweyer, Geert; Hoischen, Alexander; Huyghe, Jeroen R; Raes, Ann; Matthys, Erve; Sys, Emiel; Azou, Myriam; Gubler, Marie-Claire; Praet, Marleen; Van Camp, Guy; McFadden, Kelsey; Pediaditakis, Igor; Přistoupilová, Anna; Hodaňová, Kateřina; Vyleťal, Petr; Hartmannová, Hana; Stránecký, Viktor; Hůlková, Helena; Barešová, Veronika; Jedličková, Ivana; Sovová, Jana; Hnízda, Aleš; Kidd, Kendrah; Bleyer, Anthony J; Spong, Richard S; Vande Walle, Johan; Mortier, Geert; Brunner, Han; Van Laer, Lut; Kmoch, Stanislav; Katsanis, Nicholas; Loeys, Bart L

    2016-07-07

    Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We report on two families with ADTKD and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. Ultrasound and kidney biopsy revealed small dysplastic kidneys with cysts and tubular atrophy with secondary glomerular sclerosis, respectively. Exclusion of known ADTKD genes coupled with linkage analysis, whole-exome sequencing, and targeted re-sequencing identified heterozygous missense variants in SEC61A1-c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly)-both affecting functionally important and conserved residues in SEC61. Both transiently expressed SEC6A1A variants are delocalized to the Golgi, a finding confirmed in a renal biopsy from an affected individual. Suppression or CRISPR-mediated deletions of sec61al2 in zebrafish embryos induced convolution defects of the pronephric tubules but not the pronephric ducts, consistent with the tubular atrophy observed in the affected individuals. Human mRNA encoding either of the two pathogenic alleles failed to rescue this phenotype as opposed to a complete rescue by human wild-type mRNA. Taken together, these findings provide a mechanism by which mutations in SEC61A1 lead to an autosomal-dominant syndromic form of progressive chronic kidney disease. We highlight protein translocation defects across the endoplasmic reticulum membrane, the principal role of the SEC61 complex, as a contributory pathogenic mechanism for ADTKD.

  20. Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases.

    PubMed

    Ye, Lin; Chang, Judy C; Lin, Chin; Sun, Xiaofang; Yu, Jingwei; Kan, Yuet Wai

    2009-06-16

    The innovation of reprogramming somatic cells to induced pluripotent stem cells provides a possible new approach to treat beta-thalassemia and other genetic diseases such as sickle cell anemia. Induced pluripotent stem (iPS) cells can be made from these patients' somatic cells and the mutation in the beta-globin gene corrected by gene targeting, and the cells differentiated into hematopoietic cells to be returned to the patient. In this study, we reprogrammed the skin fibroblasts of a patient with homozygous beta(0) thalassemia into iPS cells, and showed that the iPS cells could be differentiated into hematopoietic cells that synthesized hemoglobin. Prenatal diagnosis and selective abortion have been effective in decreasing the number of beta-thalassemia births in some countries that have instituted carrier screening and genetic counseling. To make use of the cells from the amniotic fluid or chorionic villus sampling that are used for prenatal diagnosis, we also showed that these cells could be reprogrammed into iPS cells. This raises the possibility of providing a new option following prenatal diagnosis of a fetus affected by a severe illness. Currently, the parents would choose either to terminate the pregnancy or continue it and take care of the sick child after birth. The cells for prenatal diagnosis can be converted into iPS cells for treatment in the perinatal periods. Early treatment has the advantage of requiring much fewer cells than adult treatment, and can also prevent organ damage in those diseases in which damage can begin in utero or at an early age.

  1. EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia

    PubMed Central

    Little, Courtney R; Reid, Marvin E; Soares, Deanne P; Taylor-Bryan, Carolyn; Knight-Madden, Jennifer M; Stuber, Susan E; Badaloo, Asha V; Aldred, Karen; Wisdom-Phipps, Margaret E; Latham, Teresa; Ware, Russell E

    2016-01-01

    Background Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown. Objective The primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function. Methods This prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months. Results Currently, 43 participants have been enrolled out of a projected 50. There was one

  2. Acquired aplastic anemia.

    PubMed

    Keohane, Elaine M

    2004-01-01

    Acquired aplastic anemia (AA) is a disorder characterized by a profound deficit of hematopoietic stem and progenitor cells, bone marrow hypocellularity, and peripheral blood pancytopenia. It primarily affects children, young adults, and those over 60 years of age. The majority of cases are idiopathic; however, idiosyncratic reactions to some drugs, chemicals, and viruses have been implicated in its etiology. An autoimmune T-cell reaction likely causes the stem cell depletion, but the precise mechanism, as well as the eliciting and target antigens, is unknown. Symptoms vary from severe life-threatening cytopenias to moderate or non-severe disease that does not require transfusion support. The peripheral blood typically exhibits pancytopenia, reticulocytopenia, and normocytic or macrocytic erythrocytes. The bone marrow is hypocellular and may exhibit dysplasia of the erythrocyte precursors. First line treatment for severe AA consists of hematopoietic stem cell transplantation in young patients with HLA identical siblings, while immunosuppression therapy is used for older patients and for those of any age who lack a HLA matched donor. Patients with AA have an increased risk of developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute leukemia. Further elucidation of the pathophysiology of this disease will result in a better understanding of the interrelationship among AA, PNH, and MDS, and may lead to novel targeted therapies.

  3. The LDLR locus in Alzheimer's disease: a family-based study and meta-analysis of case-control data.

    PubMed

    Bertram, Lars; Hsiao, Monica; McQueen, Matthew B; Parkinson, Michele; Mullin, Kristina; Blacker, Deborah; Tanzi, Rudolph E

    2007-01-01

    Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population.

  4. The hepcidin-ferroportin system as a therapeutic target in anemias and iron overload disorders.

    PubMed

    Ganz, Tomas; Nemeth, Elizabeta

    2011-01-01

    The review summarizes the current understanding of the role of hepcidin and ferroportin in normal iron homeostasis and its disorders. The various approaches to therapeutic targeting of hepcidin and ferroportin in iron-overload disorders (mainly hereditary hemochromatosis and β-thalassemia) and iron-restrictive anemias (anemias associated with infections, inflammatory disorders, and certain malignancies, anemia of chronic kidney diseases, and iron-refractory iron-deficiency anemia) are also discussed.

  5. Nucleolar stress in Diamond Blackfan anemia pathophysiology.

    PubMed

    Ellis, Steven R

    2014-06-01

    Diamond Blackfan anemia is a red cell hypoplasia that typically presents within the first year of life. Most cases of Diamond Blackfan anemia are caused by ribosome assembly defects linked to haploinsufficiency for structural proteins of either ribosomal subunit. Nucleolar stress associated with abortive ribosome assembly leads to p53 activation via the interaction of free ribosomal proteins with HDM2, a negative regulator of p53. Significant challenges remain in linking this nucleolar stress signaling pathway to the clinical features of Diamond Blackfan anemia. Defining aspects of disease presentation may relate to developmental and physiological triggers that work in conjunction with nucleolar stress signaling to heighten the p53 response in the developing erythron after birth. The growing number of ribosomopathies provides additional challenges for linking molecular mechanisms with clinical phenotypes. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.

  6. Assignment of the disease locus for lethal congenital contracture syndrome to a restricted region of chromosome 9q34, by genome scan using five affected individuals.

    PubMed

    Mäkelä-Bengs, P; Järvinen, N; Vuopala, K; Suomalainen, A; Ignatius, J; Sipilä, M; Herva, R; Palotie, A; Peltonen, L

    1998-08-01

    Lethal congenital contracture syndrome (LCCS) is an autosomal recessive disease leading to death before the 32d gestational week. It is characterized by the fetal akinesia phenotype, with highly focused degeneration of motoneurons in the spinal cord as the main neuropathological finding. We report here the assignment of the LCCS locus to a defined region of chromosome 9q34, between markers D9S1825 and D9S1830. The initial genome scan was performed with the DNA samples of only five affected individuals from two unrelated LCCS families. The conventional linkage analysis performed with 20 affected individuals and their families was focused on those chromosomal regions in which the affected siblings were identical by descent in the initial scan. One core haplotype of 3 cM was observed in LCCS alleles, supporting the assumption of one major mutation underlying LCCS, and linkage disequilibrium analysis restricted the critical chromosomal region to <100 kb in the vicinity of marker D9S61. Two genes, NGAL (neutrophil gelatinase-associated lipocalin and NOTCH 1, were excluded as causative genes for LCCS

  7. Clustering and age of onset in familial late onset Alzheimer`s disease are determined at the apoliopoprotein E locus

    SciTech Connect

    Houlden, H.; Rossor, M.

    1994-09-01

    Recent work has demonstrated that the apolipoprotein E (ApoE) genotype is of great importance in the etiology of Alzheimer`s disease (AD). Thus, inheritance of the ApoE4 allele predisposes to the occurrences of late onset disease and decreases the onset age in families with pathogenic mutations in the amyloid precursor protein gene. We analysed ApoE genotypes in 35 families multiply affected by AD and confirm that familial clustering in late onset AD is associated with the ApoE4 allele. This allele occurs in the great majority (82%) of late onset familial Alzheimer cases. Elderly unaffected sibs (80-90 years) have an allele frequency that is not significantly different to that of normal controls. Data presented from our family sets together previously published data is suggestive that the effect of a single ApoE4 allele is to increase the risk of developing AD by an amount equivalent to 5 years and that the effect of ApoE4 homozygosity is to increase the risk of developing AD by an amount equivalent to 10 years of age. Data shows significant difference between the frequency of the ApoE4 allele in the familial AD probands and controls and in both sets of unaffected sibs, p<0.01.

  8. Genetic basis of glycogen storage disease type 1a: Prevalent mutations at the glucose-6-phosphatase locus

    SciTech Connect

    Ke-Jian Lei; Hungwen Chen; Ji-Lan Liu

    1995-10-01

    Diagnosis of glycogen storage disease (GSD) type 1a currently is established by demonstrating the lack of glucose-6-phosphatase (G6Pase) activity in the patient`s biopsied liver specimen. Recent cloning of the G6Pase gene and identification of mutations within the gene that causes GSD type 1a allow for the development of a DNA-based diagnostic method. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 70 unrelated patients with enzymatically confirmed diagnosis of GSD type 1a and detected mutations in all except 17 alleles (88%). Sixteen mutations were uncovered that were shown by expression to abolish or greatly reduce G6Pase activity and that therefore are responsible for the GSD type la disorder. R83C and Q347X are the most prevalent mutations found in Caucasians, 130X and R83C are most prevalent in Hispanics, and R83H is most prevalent in Chinese. The Q347X mutation has thus far been identified only in Caucasian patients, and the 130X mutation has been identified only in Hispanic patients. Our results demonstrate that the DNA-based analysis can accurately, rapidly, and noninvasively detect the majority of mutations in GSD type 1a. This DNA-based diagnosis now permits prenatal diagnosis among at-risk patients and serves as a database in screening and counseling patients clinically suspected of having this disease. 22 refs., 2 figs., 4 tabs.

  9. Evaluation of Macrocytic Anemias.

    PubMed

    Green, Ralph; Dwyre, Denis M

    2015-10-01

    Macrocytic anemia, defined as a mean cell volume (MCV) ≥100 fL in adults, has a narrow differential diagnosis that requires evaluation of the peripheral blood smear as well as additional laboratory testing taken in conjunction with clinical information that includes patient history and physical examination findings. This review is an update on the approach to a patient with macrocytic anemia with attention paid to the differentiation of megaloblastic and non-megaloblastic macrocytic anemias. Critical to the determination of the diagnosis is the judicious use of laboratory testing and the evaluation of those findings in conjunction with the patient medical, surgical, and medication history.

  10. Hookworm Anemia in a Peritoneal Dialysis Patient in China.

    PubMed

    Wu, Fuquan; Xu, Ying; Xia, Min; Ying, Guanghui; Shou, Zhangfei

    2016-06-01

    Hookworm infections as well as other intestinal nematodiases are endemic in China. In this case, a 70-year-old male showed symptoms of chest tightness, shortness of breath, and both lower extremities edema. The diagnostic result was chronic renal insufficiency, chronic kidney disease (5th stage), and renal anemia at first. Then, he received treatment with traditional drugs. However, this treatment did not help to alleviate the symptoms of the patient significantly. The results of gastroendoscopy showed hookworms in the duodenum, also confirmed by pathology examination. Anemia was markedly ameliorated after eliminating the parasites. The results mentioned above suggested that ancylostomiasis was the leading causes of anemia in this patient, and the etiology of anemia in uremic patients should be systematically considered. Especially when anemia could not be cured by regular treatments, rare diseases should be investigated.

  11. [Anemia of chronic disorder - pathogenesis, clinical presentation and treatment].

    PubMed

    Demarmels Biasiutti, Franziska

    2010-05-01

    After iron deficiency anemia the anemia of chronic disorder is the second most frequent anemia, and in hospitalized patients and/or patients suffering from chronic disease, especially infection, cancer and autoimmune disorders it is even the most frequent anemia. Morphologically it belongs to the normochromic, normocytic, hyporegeneratoric anemias. Pathogenetically it is induced by the upregulation of hepcidin, a recently detected acute phase protein with most important regulatory function in the iron-household. As a consequence of elevated hepcidin at the same time iron absorption in the bowel as well as iron release from macrophages are reduced, resulting in sequestration of iron in the RES and therefore functional iron deficiency. The other reason is a blunted release of erythropoetin (EPO) with at the same time reduced effectiveness due to down-regulation of EPO-receptors on erythroid cells. Treatment consists first of all in the therapy of the underlying disease and possibly in the combined application of EPO and iron.

  12. Investigation of the Genetics of Hematologic Diseases

    ClinicalTrials.gov

    2017-03-01

    Bone Marrow Failure Syndromes; Erythrocyte Disorder; Leukocyte Disorder; Hemostasis; Blood Coagulation Disorder; Sickle Cell Disease; Dyskeratosis Congenita; Diamond-Blackfan Anemia; Congenital Thrombocytopenia; Severe Congenital Neutropenia; Fanconi Anemia

  13. Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity.

    PubMed

    Hinney, Anke; Albayrak, Ozgür; Antel, Jochen; Volckmar, Anna-Lena; Sims, Rebecca; Chapman, Jade; Harold, Denise; Gerrish, Amy; Heid, Iris M; Winkler, Thomas W; Scherag, André; Wiltfang, Jens; Williams, Julie; Hebebrand, Johannes

    2014-06-01

    Deviations from normal body weight are observed prior to and after the onset of Alzheimer's disease (AD). Midlife obesity confers increased AD risk in later life, whereas late-life obesity is associated with decreased AD risk. The role of underweight and weight loss for AD risk is controversial. Based on the hypothesis of shared genetic variants for both obesity and AD, we analyzed the variants identified for AD or obesity from genome-wide association meta-analyses of the GERAD (AD, cases = 6,688, controls = 13,685) and GIANT (body mass index [BMI] as measure of obesity, n = 123,865) consortia. Our cross-disorder analysis of genome-wide significant 39 obesity SNPs and 23 AD SNPs in these two large data sets revealed that: (1) The AD SNP rs10838725 (pAD  = 1.1 × 10(-08)) at the locus CELF1 is also genome-wide significant for obesity (pBMI  = 7.35 × 10(-09) ). (2) Four additional AD risk SNPs were nominally associated with obesity (rs17125944 at FERMT2, pBMI  = 4.03 × 10(-05), pBMI corr  = 2.50 × 10(-03) ; rs3851179 at PICALM; pBMI  = 0.002, rs2075650 at TOMM40/APOE, pBMI  = 0.024, rs3865444 at CD33, pBMI  = 0.024). (3) SNPs at two of the obesity risk loci (rs4836133 downstream of ZNF608; pAD  = 0.002 and at rs713586 downstream of RBJ/DNAJC27; pAD  = 0.018) were nominally associated with AD risk. Additionally, among the SNPs used for confirmation in both studies the AD risk allele of rs1858973, with an AD association just below genome-wide significance (pAD  = 7.20 × 10(-07)), was also associated with obesity (SNP at IQCK/GPRC5B; pBMI  = 5.21 × 10(-06) ; pcorr  = 3.24 × 10(-04)). Our first GWAS based cross-disorder analysis for AD and obesity suggests that rs10838725 at the locus CELF1 might be relevant for both disorders.

  14. Association of rs10757274 and rs2383206 Polymorphisms on 9p21 locus with Coronary Artery Disease in Turkish Population

    PubMed Central

    Okyay, Kaan; Yılmaz, Akın; Şahinarslan, Asife; Yar Sağlam, Atiye Seda; Eyiol, Azmi; Bolayır, Hasan Ata; Sezenöz, Burak; Menevşe, Sevda; Çengel, Atiye

    2016-01-01

    Background and Objectives Genetic predisposition is an important risk factor for coronary artery disease (CAD). In this study, we aimed to evaluate the impact of rs10757274 and rs2383206 polymorphisms in chromosome 9p21 on presence and severity of CAD in a Turkish population. Subjects and Methods A total of 646 patients who underwent coronary angiography were included in this study. Coronary vessel score and Gensini score were calculated to assess the angiographic severity of CAD. Alleles of AA, AG, and GG were determined for rs10757274 (polymorphism-1) and rs2383206 (polymorphism-2) polymorphisms located in chromosome 9p21 from the blood samples. Results There was a significant difference between the alleles in polymorphism-1 in the presence of coronary artery disease (38.9% in AA, 48.0% in GG and 56.4% in AG, p=0.017). However, there was no difference between the alleles in polymorphism-2. According to vessel scores, there was a significant difference between the alleles in polymorphism-1 (AA 0.71±1.04, GG 0.88±1.07, AG 1.06±1.12, p=0.018). In polymorphism-2, vessel scores did not show a difference between the alleles. In polymorphism-1, there was a significant difference in Gensini score (p=0.041). Gensini scores did not differ between the alleles in polymorphism-2 (p>0.05 for all). In multivariate analyses, none of the alleles was an independent factor for presence of CAD. Conclusion The presence of rs10757274 polymorphism including AG allele in chromosome 9p21 was related to CAD. However, this relationship was not independent of other cardiovascular risk factors. PMID:27721851

  15. Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Aplastic Anemia Study Group.

    PubMed

    Shapiro, S; Issaragrisil, S; Kaufman, D W; Anderson, T; Chansung, K; Thamprasit, T; Sirijirachai, J; Piankijagum, A; Porapakkham, Y; Vannasaeng, S; Leaverton, P E; Young, N S

    1999-04-01

    Agranulocytosis, a syndrome characterized by a marked reduction in circulating granulocytes, is strongly associated with medical drug use in Europe and the United States. Unregulated use of common pharmaceutical agents in developing countries has been suspected of causing large numbers of cases of agranulocytosis and deaths, especially among children. To elucidate the incidence and etiology of agranulocytosis in Thailand, a population-based case-control study of symptomatic agranulocytosis that resulted in hospital admission was conducted in Bangkok from 1990 to 1994. An attempt was also made to study the disease in Khonkaen (in northeastern Thailand) and Songkla (in southern Thailand), but there were insufficient cases in the latter regions, and the analysis was confined to subjects from Bangkok. In that region, the overall incidence of agranulocytosis was 0.8 per million per year; there were no deaths. As expected, the incidence was higher in females (0.9 per million), and it increased with age (4.3 per million beyond age 60). Among 25 cases and 529 controls the relative risk estimate for a combined category of all suspect drugs was 9.2 (95% confidence interval = 3.9-21), and the proportion of cases that could be attributed to drug use was 68%. For individual drugs and drug classes the data were sparse; within these limitations, the strongest association appeared to be with antithyroid drugs. One case and three controls were exposed to dipyrone, a drug known to cause agranulocytosis; with such scanty data the risk could not be evaluated. Exposure to pesticides or solvents was not associated with an increased risk. This is the first formal epidemiologic study of agranulocytosis in a developing country. As in the West, most cases are attributable to medical drug use. However, the incidence of agranulocytosis in Bangkok, and apparently, in Thailand as a whole, is unusually low, and the disease does not pose a public health risk.

  16. [Structural analysis for psychosocial factors including health locus of control (HLC) and sense of coherence (SOC) associated with lifestyle-related diseases].

    PubMed

    Ogawa, Y; Nakamura, H; Nagase, H; Ogino, K; Ooshita, Y; Tsukahara, S

    2001-01-01

    The purpose of this study was to clarify psychosocial characteristics associated with preventive health behavior for lifestyle-related diseases. The author performed objective health examinations and gave questionnaires to 289 men (39.7 +/- 11.8 years, mean +/- SD) and 80 women (32.8 +/- 10.4 years) engaged in office work. Psychosocial factors included lifestyle and perceived stress, as well as the health locus of control (HLC) and sense of coherence (SOC) as newly developed indicators for health behavior. The principal component analysis for men did not extract lifestyle from the psychosocial structures. Multiple regression analysis showed that internal HLC (IHLC), chance HLC (CHLC), professional HLC (PHLC) and stress significantly contributed to SOC. Principal component analysis using psychosocial factors in women showed two psychosocial structures, i.e. the second principal (high SOC, high lifestyle, and low stress) and the 4th principal components (high supernatural HLC, and high PHLC). Both components were negatively correlated with systolic blood pressure. SOC was recognized to be negatively associated with age, stress, and total cholesterol, and positively with IHLC, FHLC, lifestyle, and gamma-GTP using multiple regression analysis for women. These results indicated a distinguishable sex difference regarding the involvement of psychosocial factors including HLC and SOC in objective health. SOC seems likely to be involved not in objective health, but closely with stress, suggesting a direct influence on mental health. Lifestyle should be divided into more detailed categories such as smoking and salt intake. Structural analysis of women suggests that SOC is involved directly or indirectly through lifestyle in objective health, different from men. To further clarify causal relationships between psychosocial factors and risk factors for lifestyle-related diseases, a longitudinal study is necessary based on these results.

  17. Initial diagnosis of anemia from sore mouth and improved classification of anemias by MCV and RDW in 30 patients.

    PubMed

    Lu, Shin-Yu; Wu, Hong-Cheng

    2004-12-01

    Thirty patients with a wide range of sore mouth that led to the diagnosis of iron deficiency in 12 patients, pernicious anemia in 8 patients, combined deficiency of iron and vitamin B12 in 2 patients, and anemia of chronic disease in 8 patients were investigated. The oral signs and symptoms included glossitis, glossodynia, angular cheilitis, recurrent oral ulcer, oral candidosis, diffuse erythematous mucositis, and pale oral mucosa. The values of hemoglobin in 30 patients varied from normal to severe life-threatening levels, but none had developed generalized symptoms sufficiently advanced to arouse suspicions of anemia before they visited the Oral Medicine Clinic. The aim of this paper is to describe a retrospective study of 30 patients with oral changes as the initial manifestation of nutritional deficiency or anemia of chronic diseases. Improved diagnosis and classification of anemia based on the mean and heterogeneity of red cell size will be discussed.

  18. Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation.

    PubMed

    Gerull, Sabine; Stern, Martin; Apperley, Jane; Beelen, Dietrich; Brinch, Lorentz; Bunjes, Donald; Butler, Andrew; Ganser, Arnold; Ghavamzadeh, Ardeshir; Koh, Mickey B; Komarnicki, Mieczyslaw; Kröger, Nicolaus; Maertens, Johan; Maschan, Alexei; Peters, Christina; Rovira, Montserrat; Sengeløv, Henrik; Socié, Gerard; Tischer, Johanna; Oneto, Rosi; Passweg, Jakob; Marsh, Judith

    2013-11-01

    Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source.

  19. Living with Fanconi Anemia

    MedlinePlus

    ... from the NHLBI on Twitter. Living With Fanconi Anemia Improvements in blood and marrow stem cell transplants ... November 1, 2011 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA NO FEAR ACT OIG ...

  20. Anemia and heart failure.

    PubMed

    O'Meara, Eileen; Murphy, Clare; McMurray, John J V

    2004-12-01

    Over the past few years, anemia has emerged as a powerful independent predictor of adverse outcomes in chronic heart failure (CHF). It affects up to 50% of patients with CHF, depending on the definition of anemia used and on the population studied. Even small reductions in hemoglobin are associated with worse outcome. However, the causes of anemia in CHF remain unclear, although impairment of renal function and inflammatory cytokines are proposed mechanisms. Both may act through impairment of the synthesis or action of erythropoietin. Preliminary studies have demonstrated improvement in symptoms, exercise tolerance, quality of life, and reductions in hospitalizations when patients with severe CHF were treated with erythropoietin. The benefits and the potential risks of such therapies will be further addressed in upcoming larger randomized trials. The recent interest in anemia reflects a new perspective in heart failure therapy, focusing on non-cardiovascular comorbidities.

  1. Your Guide to Anemia

    MedlinePlus

    ... essential compounds. It also helps regulate your body temperature, fights infection, and gets rid of waste products. ... Some AIHA antibodies become active only in warm temperatures; others only in cold temperatures. – Alloimmune hemolytic anemia. ...

  2. Genetic modulation of sickle cell anemia

    SciTech Connect

    Steinberg, M.H.

    1995-05-01

    Sickle cell anemia, a common disorder associated with reduced life span of the red blood cell and vasoocclusive events, is caused by a mutation in the {Beta}-hemoglobin gene. Yet, despite this genetic homogeneity, the phenotype of the disease is heterogeneous. This suggests the modulating influence of associated inherited traits. Some of these may influence the accumulation of fetal hemoglobin, a hemoglobin type that interferes with the polymerization of sickle hemoglobin. Another inherited trait determines the accumulation of {alpha}-globin chains. This review focuses on potential genetic regulators of the phenotype of sickle cell anemia. 125 refs., 6 figs., 3 tabs.

  3. Idiopathic aplastic anemia: diagnosis and classification.

    PubMed

    Dolberg, Osnat Jarchowsky; Levy, Yair

    2014-01-01

    Aplastic anemia (AA) is a disease characterized by pancytopenia and hypoplastic bone marrow caused by the decrease of hematopoietic stem cells. The pathogenesis of AA is complex and involves an abnormal hematopoietic microenvironment, hematopoietic stem cell/progenitor cell deficiencies and immunity disorders. Survival in severe aplastic anemia (SAA) has markedly improved in the past 4 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive and biologic drugs, and supportive care. Herein, we will update the main issues concern AA according to our literature review.

  4. The Prevalence of Anemia and Moderate-Severe Anemia in the US Population (NHANES 2003-2012)

    PubMed Central

    2016-01-01

    Since anemia is associated with poor health outcomes, the prevalence of anemia is a significant public health indicator. Even though anemia is primarily caused by iron deficiency, low oxygen-carrying capacity may result from other conditions such as chronic diseases, which remain a relevant health concern in the United States. However, studies examining current rates of anemia in the total US population and in more specific subgroups are limited. Data from five National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2012 were analyzed to assess two outcomes: anemia and moderate-severe anemia, which were based upon serum hemoglobin levels (Hb) as per World Health Organization (WHO) definitions. Statistical analysis using SAS examined temporal trends and the prevalence of anemia among sexes, age groups, and races/ethnicities. The study estimated that an average of 5.6% of the U.S. population met the criteria for anemia and 1.5% for moderate-severe anemia during this 10-year period. High-risk groups such as pregnant women, elderly persons, women of reproductive age, non-Hispanic blacks, and Hispanics were identified, and relationships between multiple risk factors were examined. Rates of anemia in men increased monotonically with age, while that of women increased bimodally with peaks in age group 40–49 years and 80–85 years. The effect of risk factors was observed to compound. For instance, the prevalence of anemia in black women aged 80–85 years was 35.6%, 6.4 times higher than the population average. Moreover, anemia is a growing problem because of the increased prevalence of anemia (4.0% to 7.1%) and moderate-severe anemia (1.0% to 1.9%), which nearly doubled from 2003–2004 to 2011–2012. Thus, these results augment the current knowledge on anemia prevalence, severity, and distribution among subgroups in the US and raised anemia as an issue that requires urgent public health intervention. PMID:27846276

  5. How Is Iron-Deficiency Anemia Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Is Iron-Deficiency Anemia Treated? Treatment for iron-deficiency anemia will depend ... may be advised. Treatments for Severe Iron-Deficiency Anemia Blood Transfusion If your iron-deficiency anemia is ...

  6. [Treatment of anemia in hip fracture surgery].

    PubMed

    García Pascual, E

    2015-06-01

    Repairing hip fractures is one of the most common surgical procedures and has greater morbidity and mortality. This procedure is also a process that involves a greater need for blood products. Numerous factors influence morbidity, mortality and the use of blood products: patient age, concomitant diseases and drug treatments that change hemostasis and hemorrhaging (preoperative, intraoperative and postoperative), which are usually significant. On top of all this is the presence in a high percentage of cases of preoperative anemia, which can have one or more causes. It is therefore essential to establish an appropriate management of perioperative anemia and optimize the transfusion policy. The aim of this review is to briefly analyze the epidemiology of hip fractures as well as establish a basis for treating perioperative anemia and transfusion policies, proposing guidelines and recommendations for clinical management based on the most current studies.

  7. Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease

    PubMed Central

    Johnson, Matthew P.; Brennecke, Shaun P.; East, Christine E.; Dyer, Thomas D.; Roten, Linda T.; Proffitt, J. Michael; Melton, Phillip E.; Fenstad, Mona H.; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K.; Pouta, Anneli; Kivinen, Katja; Ekholm, Eeva; Hietala, Reija; Sainio, Susanna; Saisto, Terhi; Uotila, Jukka; Klemetti, Miira; Inkeri Lokki, Anna; Georgiadis, Leena; Huovari, Elina; Kortelainen, Eija; Leminen, Satu; Lähdesmäki, Aija; Mehtälä, Susanna; Salmen, Christina

    2013-01-01

    Pre-eclampsia is an idiopathic pregnancy disorder promoting morbidity and mortality to both mother and child. Delivery of the fetus is the only means to resolve severe symptoms. Women with pre-eclamptic pregnancies demonstrate increased risk for later life cardiovascular disease (CVD) and good evidence suggests these two syndromes share several risk factors and pathophysiological mechanisms. To elucidate the genetic architecture of pre-eclampsia we have dissected our chromosome 2q22 susceptibility locus in an extended Australian and New Zealand familial cohort. Positional candidate genes were prioritized for exon-centric sequencing using bioinformatics, SNPing, transcriptional profiling and QTL-walking. In total, we interrogated 1598 variants from 52 genes. Four independent SNP associations satisfied our gene-centric multiple testing correction criteria: a missense LCT SNP (rs2322659, P = 0.0027), a synonymous LRP1B SNP (rs35821928, P = 0.0001), an UTR-3 RND3 SNP (rs115015150, P = 0.0024) and a missense GCA SNP (rs17783344, P = 0.0020). We replicated the LCT SNP association (P = 0.02) and observed a borderline association for the GCA SNP (P = 0.07) in an independent Australian case–control population. The LRP1B and RND3 SNP associations were not replicated in this same Australian singleton cohort. Moreover, these four SNP associations could not be replicated in two additional case–control populations from Norway and Finland. These four SNPs, however, exhibit pleiotropic effects with several quantitative CVD-related traits. Our results underscore the genetic complexity of pre-eclampsia and present novel empirical evidence of possible shared genetic mechanisms underlying both pre-eclampsia and other CVD-related risk factors. PMID:23420841

  8. Use Massive Parallel Sequencing and Exome Capture Technology to Sequence the Exome of Fanconi Anemia Children and Their Patents

    ClinicalTrials.gov

    2013-11-21

    Fanconi Anemia; Autosomal or Sex Linked Recessive Genetic Disease; Bone Marrow Hematopoiesis Failure, Multiple Congenital Abnormalities, and Susceptibility to Neoplastic Diseases.; Hematopoiesis Maintainance.

  9. Anemia in hospitalized patients with pulmonary tuberculosis*

    PubMed Central

    Oliveira, Marina Gribel; Delogo, Karina Neves; de Oliveira, Hedi Marinho de Melo Gomes; Ruffino-Netto, Antonio; Kritski, Afranio Lineu; Oliveira, Martha Maria

    2014-01-01

    OBJECTIVE: To describe the prevalence of anemia and of its types in hospitalized patients with pulmonary tuberculosis. METHODS: This was a descriptive, longitudinal study involving pulmonary tuberculosis inpatients at one of two tuberculosis referral hospitals in the city of Rio de Janeiro, Brazil. We evaluated body mass index (BMI), triceps skinfold thickness (TST), arm muscle area (AMA), ESR, mean corpuscular volume, and red blood cell distribution width (RDW), as well as the levels of C-reactive protein, hemoglobin, transferrin, and ferritin. RESULTS: We included 166 patients, 126 (75.9%) of whom were male. The mean age was 39.0 ± 10.7 years. Not all data were available for all patients: 18.7% were HIV positive; 64.7% were alcoholic; the prevalences of anemia of chronic disease and iron deficiency anemia were, respectively, 75.9% and 2.4%; and 68.7% had low body weight (mean BMI = 18.21 kg/m2). On the basis of TST and AMA, 126 (78.7%) of 160 patients and 138 (87.9%) of 157 patients, respectively, were considered malnourished. Anemia was found to be associated with the following: male gender (p = 0.03); low weight (p = 0.0004); low mean corpuscular volume (p = 0.03);high RDW (p = 0; 0003); high ferritin (p = 0.0005); and high ESR (p = 0.004). We also found significant differences between anemic and non-anemic patients in terms of BMI (p = 0.04), DCT (p = 0.003), and ESR (p < 0.001). CONCLUSIONS: In this sample, high proportions of pulmonary tuberculosis patients were classified as underweight and malnourished, and there was a high prevalence of anemia of chronic disease. In addition, anemia was associated with high ESR and malnutrition. PMID:25210963

  10. How I Diagnose Non-thalassemic Microcytic Anemias.

    PubMed

    Bruno, Mariasole; De Falco, Luigia; Iolascon, Achille

    2015-10-01

    Microcytic anemia is the most common form of anemia, characterized by reduced hemoglobin (Hb) synthesis associated with decreased red blood cell volume (MCV). It is a very heterogeneous group of diseases that may be either acquired or inherited. Microcytic hypochromic anemia can result from defects in globin (hemoglobinopathies or thalassemias) or heme synthesis or in iron availability, or acquisition by the erythroid precursors. Diagnosis of microcytic anaemia appears to be important in children/adolescents, especially to set, where possible, a treatment plan on the basis of the etiology and pathogenesis. After excluding the acquired causes of microcytic anemia that represent the most frequent etiology, according to the differential diagnosis, the analysis of genetic causes, mostly hereditary, must be considered. This review will consider acquired and hereditary microcytic anemias due to heme synthesis or to iron metabolism defects and their diagnosis.

  11. Investigational drugs in sickle cell anemia.

    PubMed

    Kotiah, Sandy D; Ballas, Samir K

    2009-12-01

    Sickle cell anemia is one of the most common autosomal recessive diseases in the world. Patients with sickle cell anemia have variable penetrance and it is hard to predict the risk and timing of complications. It is characterized by a point mutation in the beta-globin gene (GAG --> GTG) and the production of hemoglobin S. The latter leads to decreased deformability of the red blood cells (RBCs) that adhere to endothelia cells culminating in vascular occlusion and its sequelae of tissue ischemia and organ damage. Moreover, sickled RBCs undergo intravascular hemolysis and accelerated erythropoesis. The hallmarks of this disease are shortened RBC survival and vaso-occlusive crises. For the past ten years, the pathophysiology of this disease has been better elucidated and has led to significant improvements in the standard of care. Vaso-occlusion is now understood to be a complex event that involves abnormal interactions between RBCs, leukocytes, endothelial cells and the coagulation pathways. The field of translational research in sickle cell anemia has expanded greatly and has led to new clinical trials with new therapeutic agents and strategies. In this paper, we review the drugs that are now being investigated in the treatment of sickle cell anemia.

  12. Anemia in the emergency department: evaluation and treatment.

    PubMed

    Janz, Timothy G; Johnson, Roy L; Rubenstein, Scott D

    2013-11-01

    Anemia is a common worldwide problem that is associated with nonspecific complaints. The initial focus for the emergency evaluation of anemia is to determine whether the problem is acute or chronic. Acute anemia is most commonly associated with blood loss, and the patient is usually symptomatic. Chronic anemia is usually well tolerated and is often discovered coincidentally. Once diagnosed, the etiology of anemia can often be determined by applying a systematic approach to its evaluation. The severity of the anemia impacts clinical outcomes, particularly in critically ill patients; however, the specific threshold to transfuse is uncertain. Evaluation of the current literature and clinical guidelines does not settle this controversy, but it does help clarify that a restrictive transfusion strategy (ie, for patients with a hemoglobin < 6-8 g/dL) is associated with better outcomes than a more liberal transfusion strategy. Certain anemias may have well-defined treatment options (eg, sickle cell disease), but empiric use of nutritional supplements to treat anemia of uncertain etiology is discouraged.

  13. Treatment of iron deficiency anemia with Ferro-Folgamma.

    PubMed

    Ghinea, Mihaela Maria

    2004-01-01

    Iron deficiency anemia is a hypochromic anemia in which hemoglobin poor synthesis is due to a decrease in the amount of iron in the body. The decrease of iron quantity has many causes: insufficient intake of aliments rich in iron (meat, viscera, green vegetables), increased necessities during growth period, pregnancy, erythrocytes hyperregeneration, high-performance sportsmen, increased loss by digestive way, genito-urinary way, respiratory, hemorrhagic syndromes. Clinically, symptoms and signs specific to all types of anemia and those specific to lack of iron occur besides the symptoms and signs of the underlying disease: atrophic glositis, angular stomatitis, sideropenic dysphagia, pica, skin and nails changes. Laboratory investigations useful for diagnosis are: microcytic, hypochromic anemia, decreased serum iron level, total capacity of iron binding increased, medullar iron store absent, good response to iron therapy. Ferro-Folgamma is one of the most indicated medicines in iron deficiency anemia. Due to its components this medicine has many indications: insufficient alimentary intake concerning iron, folic acid, B12 vitamin, vegetarian alimentation, increased needs during growth period, iron deficiency anaemia secondary to chronic hemorrhages, malnutrition, anemias associated with chronic alcohol intake, preventive treatment of iron deficiency anemia and megaloblastic anemia during pregnancy and lactation.

  14. Factors Associated with Anemia in the Institutionalized Elderly

    PubMed Central

    da Silva, Emanuelle Cruz; Roriz, Anna Karla Carneiro; Eickemberg, Michaela; Mello, Adriana Lima; Côrtes, Elvira Barbosa Quadros; Feitosa, Caroline Alves; Medeiros, Jairza Maria Barreto; Ramos, Lílian Barbosa

    2016-01-01

    As a common problem in long-term care facilities (LTCFs), anemia affects 25–63% of the elderly. The aim of the present study was to describe the prevalence and characteristics of anemia and its associated factors in the institutionalized elderly. The cross-sectional study was carried out with three hundred thirteen individuals aged ≥ 60 years, of both genders, living in long-term care facilities for the elderly in Salvador, Bahia, Brazil. Poisson regression (PR) with robust variance estimates was used to assess the factors related to anemia. The prevalence of anemia was 38%. Mild anemia was predominant in both genders (male: 26.8%; female: 21.1%), as normocytic and normochromic anemia, with no anisocytosis (69.75%). Anemia was associated with thinness (PR: 1.68; 95% CI: 1.04–2.72) and with moderate (PR: 1.98; 95% CI: 1.07–3.63) and total (PR: 2.61; 95% CI: 1.34–5.07) dependence in the final model. Severe dependence exhibited borderline significance (PR: 1.94; 95% CI: 1.00–3.77). The prevalence of anemia was high in the institutionalized elderly in both genders, with characteristics suggesting chronic diseases as the causal factor, and the frequency of occurrence was higher in thinness elderly with moderate to total dependence. PMID:27607057

  15. Factors Associated with Anemia in the Institutionalized Elderly.

    PubMed

    Silva, Emanuelle Cruz da; Roriz, Anna Karla Carneiro; Eickemberg, Michaela; Mello, Adriana Lima; Côrtes, Elvira Barbosa Quadros; Feitosa, Caroline Alves; Medeiros, Jairza Maria Barreto; Ramos, Lílian Barbosa

    2016-01-01

    As a common problem in long-term care facilities (LTCFs), anemia affects 25-63% of the elderly. The aim of the present study was to describe the prevalence and characteristics of anemia and its associated factors in the institutionalized elderly. The cross-sectional study was carried out with three hundred thirteen individuals aged ≥ 60 years, of both genders, living in long-term care facilities for the elderly in Salvador, Bahia, Brazil. Poisson regression (PR) with robust variance estimates was used to assess the factors related to anemia. The prevalence of anemia was 38%. Mild anemia was predominant in both genders (male: 26.8%; female: 21.1%), as normocytic and normochromic anemia, with no anisocytosis (69.75%). Anemia was associated with thinness (PR: 1.68; 95% CI: 1.04-2.72) and with moderate (PR: 1.98; 95% CI: 1.07-3.63) and total (PR: 2.61; 95% CI: 1.34-5.07) dependence in the final model. Severe dependence exhibited borderline significance (PR: 1.94; 95% CI: 1.00-3.77). The prevalence of anemia was high in the institutionalized elderly in both genders, with characteristics suggesting chronic diseases as the causal factor, and the frequency of occurrence was higher in thinness elderly with moderate to total dependence.

  16. A novel ubiquitin ligase is deficient in Fanconi anemia.

    PubMed

    Meetei, Amom Ruhikanta; de Winter, Johan P; Medhurst, Annette L; Wallisch, Michael; Waisfisz, Quinten; van de Vrugt, Henri J; Oostra, Anneke B; Yan, Zhijiang; Ling, Chen; Bishop, Colin E; Hoatlin, Maureen E; Joenje, Hans; Wang, Weidong

    2003-10-01

    Fanconi anemia is a recessively inherited disease characterized by congenital defects, bone marrow failure and cancer susceptibility. Cells from individuals with Fanconi anemia are highly sensitive to DNA-crosslinking drugs, such as mitomycin C (MMC). Fanconi anemia proteins function in a DNA damage response pathway involving breast cancer susceptibility gene products, BRCA1 and BRCA2 (refs. 1,2). A key step in this pathway is monoubiquitination of FANCD2, resulting in the redistribution of FANCD2 to nuclear foci containing BRCA1 (ref. 3). The underlying mechanism is unclear because the five Fanconi anemia proteins known to be required for this ubiquitination have no recognizable ubiquitin ligase motifs. Here we report a new component of a Fanconi anemia protein complex, called PHF9, which possesses E3 ubiquitin ligase activity in vitro and is essential for FANCD2 monoubiquitination in vivo. Because PHF9 is defective in a cell line derived from an individual with Fanconi anemia, we conclude that PHF9 (also called FANCL) represents a novel Fanconi anemia complementation group (FA-L). Our data suggest that PHF9 has a crucial role in the Fanconi anemia pathway as the likely catalytic subunit required for monoubiquitination of FANCD2.

  17. Could Anemia Cause Hearing Loss?

    MedlinePlus

    ... fullstory_162793.html Could Anemia Cause Hearing Loss? Iron deficiency might keep ear cells from getting oxygen ... HealthDay News) -- Hearing loss may be linked to iron deficiency anemia -- a combination of low levels of ...

  18. Inborn anemias in mice: (Annual report, 1980-1981)

    SciTech Connect

    Bernstein, S.E.

    1981-07-02

    The basic purpose of this study is the delineation and exploitation of inborn anemias of the laboratory mouse, carried out by utilization of genetically homogeneous stocks segregating only for anemia-producing genes; by physiological and histological descriptions of each condition at all stages in the life history; by determination of tissue sites of primary gene action through tissue culture studies, tissue transplantation and parabiosis experiments; by analysis of reactions of normal and anemic mice to a variety of stressful stimuli, including x-irradiation, hypoxia, and toxic chemicals, and by biochemical comparisons between tissues, especially erythrocytes and hemopoietic cells of normal vs each type of anemic mouse. At present 16 single-locus anemias are known in the mouse, plus one with multifactorial inheritance (the autoimmune hemolytic anemia of NZB inbred mice). Of these, six are maintained only by the Jackson Laboratory, and two others have but one additional source. Effects of anemia-producing mutant alleles of these loci (an; f; ja; ha; Hba/sup th/; mk; nb; Sl and Sl/sup d/; sla; sph; and W, W/sup v/, W/sup J/ and 10 other putative W-alleles) are currently under investigation at the Jackson Laboratory. 15 refs.

  19. Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

    PubMed Central

    Lang, Elisabeth; Gatidis, Sergios; Freise, Noemi F; Bock, Hans; Kubitz, Ralf; Lauermann, Christian; Orth, Hans Martin; Klindt, Caroline; Schuier, Maximilian; Keitel, Verena; Reich, Maria; Liu, Guilai; Schmidt, Sebastian; Xu, Haifeng C; Qadri, Syed M; Herebian, Diran; Pandyra, Aleksandra A; Mayatepek, Ertan; Gulbins, Erich; Lang, Florian; Häussinger, Dieter; Lang, Karl S; Föller, Michael; Lang, Philipp A

    2015-01-01

    Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca2+ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Conclusion: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (Hepatology 2015;61:275–284) PMID:25065608

  20. Mechanisms of anemia in CKD.

    PubMed

    Babitt, Jodie L; Lin, Herbert Y

    2012-10-01

    Anemia is a common feature of CKD associated with poor outcomes. The current management of patients with anemia in CKD is controversial, with recent clinical trials demonstrating increased morbidity and mortality related to erythropoiesis stimulating agents. Here, we examine recent insights into the molecular mechanisms underlying anemia of CKD. These insights hold promise for the development of new diagnostic tests and therapies that directly target the pathophysiologic processes underlying this form of anemia.

  1. [Autoimmune hemolytic anemia in children].

    PubMed

    Becheur, M; Bouslama, B; Slama, H; Toumi, N E H

    2015-01-01

    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options.

  2. Vitamin B12 deficiency anemia

    MedlinePlus

    ... body tissues. There are many types of anemia. Vitamin B12 deficiency anemia is a low red blood cell count ... anemia often do well with treatment. Long-term vitamin B12 deficiency can cause nerve damage. This may be permanent ...

  3. How Is Aplastic Anemia Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Aplastic Anemia Diagnosed? Your doctor will diagnose aplastic anemia based on your medical and family histories, a ... your primary care doctor thinks you have aplastic anemia, he or she may refer you to a ...

  4. How Is Fanconi Anemia Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Fanconi Anemia Diagnosed? People who have Fanconi anemia (FA) are born with the disorder. They may ... questions about: Any personal or family history of anemia Any surgeries you’ve had related to the ...

  5. How Is Fanconi Anemia Treated?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Fanconi Anemia Treated? Doctors decide how to treat Fanconi anemia (FA) based on a person's age and how ... Long-term treatments for FA can: Cure the anemia. Damaged bone marrow cells are replaced with healthy ...

  6. [THE DIFFERENTIAL DIAGNOSTIC POSSIBILITIES IN EVALUATION OF IRON-DEFICIENT CONDITION UNDER ANEMIAS].

    PubMed

    Zubrikhina, G N; Blindar, V N; Matveeva, I I

    2016-03-01

    The article presents data concerning differential diagnostic possibilities of evaluation of genuine iron-deficient anemia and anemia of chronic diseases. The variety of mechanisms of development of anemia of chronic diseases is demonstrated, including effect of humoral inhibitors of erythropoiesis, disorder of iron metabolism at the expense of its redistribution into cells of macrophage system, suppression of erythropoiesis resulted in redistributed or functional iron deficiency. The data is presented concerning significance in diagnostic of anemia of chronic diseases of such factors as content of ferritin, dissolving receptors of transferrin and role of hepcidin protein in pathogenesis of anemia of chronic diseases. The analysis of scientific publications demonstrated that hepcidin is a negative regulator of iron metabolism. Under iron-deficient anemia its level in blood decreases that contribute to extensive absorption of iron in gastrointestinal tract. On the contrary, under anemia of chronic diseases its content drastically increases and results in blocking of iron transport everywhere, including internal epithelium, macrophages, placenta and other types of cells. The hyper-production of hepcidin during infection and inflammation is responsible for anemia of chronic diseases. The perspectives of development of pharmaceuticals decreasing level of hepcidin for treatment of anemia of chronic diseases is demonstrated.

  7. A short review of malabsorption and anemia.

    PubMed

    Fernández-Bañares, Fernando; Monzón, Helena; Forné, Montserrat

    2009-10-07

    Anemia is a frequent finding in most diseases which cause malabsorption. The most frequent etiology is the combination of iron and vitamin B12 deficiency. Celiac disease is frequently diagnosed in patients referred for evaluation of iron deficiency anemia (IDA), being reported in 1.8%-14.6% of patients. Therefore, duodenal biopsies should be taken during endoscopy if no obvious cause of iron deficiency (ID) can be found. Cobalamin deficiency occurs frequently among elderly patients, but it is often unrecognized because the clinical manifestations are subtle; it is caused primarily by food-cobalamin malabsorption and pernicious anemia. The classic treatment of cobalamin deficiency has been parenteral administration of the vitamin. Recent data suggest that alternative routes of cobalamin administration (oral and nasal) may be useful in some cases. Anemia is a frequent complication of gastrectomy, and has been often described after bariatric surgery. It has been shown that banding procedures which maintain digestive continuity with the antrum and duodenum are associated with low rates of ID. Helicobacter pylori (H. pylori) infection may be considered as a risk factor for IDA, mainly in groups with high demands for iron, such as some children and adolescents. Further controlled trials are needed before making solid recommendations about H. pylori eradication in these cases.

  8. [Autoimmune hemolytic anemia: diagnosis and management].

    PubMed

    Philippe, Pierre

    2007-12-01

    Autoimmune hemolytic anemia (AIHA) is diagnosed in the presence of anemia, usually macrocytic and of variable intensity, reticulocytosis, and a positive direct and/or indirect antiglobulin test, after ruling out other types of hemolytic anemia. A positive direct antiglobulin test alone is not sufficient to diagnose AIHA and may be positive in many patients without anemia or negative in some patients with AIHA. AIHA may be classified into two major categories according to the optimal temperature of antibody activity: warm-reacting autoantibodies (usually IgG) optimal around 37 degrees C and cold-reacting autoantibodies, optimal at 4 degrees C (usually IgM). This classification guides the selection of tests and treatment. AIHA is widely reported to be associated with a variety of other diseases, although these associations are often fortuitous. A minimal set of useful investigations is appropriate since AIHA may be secondary to viral infections, lymphoid malignancies, or autoimmune disorders such as lupus. Transfusion should remain rare in AHAI, but close contact with the transfusion service is necessary if it is to succeed. As for many autoimmune and/or systemic diseases, numerous types of treatment have been proposed but have not been validated in controlled multicenter studies. These are necessary to improve the management of these rare disorders.

  9. Image simulation using LOCUS

    SciTech Connect

    Strachan, J.D.; Roberts, J.A.

    1989-09-01

    The LOCUS data base program has been used to simulate images and to solve simple equations. This has been accomplished by making each record (which normally would represent a data entry)represent sequenced or random number pairs.

  10. Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

    PubMed Central

    Gerull, Sabine; Stern, Martin; Apperley, Jane; Beelen, Dietrich; Brinch, Lorentz; Bunjes, Donald; Butler, Andrew; Ganser, Arnold; Ghavamzadeh, Ardeshir; Koh, Mickey B; Komarnicki, Mieczyslaw; Kröger, Nicolaus; Maertens, Johan; Maschan, Alexei; Peters, Christina; Rovira, Montserrat; Sengeløv, Henrik; Socié, Gerard; Tischer, Johanna; Oneto, Rosi; Passweg, Jakob; Marsh, Judith

    2013-01-01

    Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source. PMID:23894010

  11. Pernicious anemia: Fundamental and practical aspects in diagnosis.

    PubMed

    Tun, Aung Myint; Thein, Kyaw Zin; Myint, Zin War; Oo, Thein Hlaing

    2017-02-03

    Pernicious anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex environmental and immunological factors. Although it was first reported by Addison in 1849 with subsequent advances in understanding of pathogenesis and molecular biology, diagnosis of pernicious anemia is still challenging for clinicians because of its complexity and diverse clinical presentations. Herein, we provide an overview of PA, mainly focusing on its scientific and practical aspects in diagnosis. We also discuss the limitations of currently available diagnostic tools for evaluation of cobalamin deficiency and PA.

  12. Anemia: Evaluation and Diagnostic Tests.

    PubMed

    Cascio, Michael J; DeLoughery, Thomas G

    2017-03-01

    Anemia is among the most common medical problems and clinical and laboratory evaluation need to be approached logically. The complete blood count with red cell indices offers clues to diagnosis. Many anemias have characteristic red cell morphology. The reticulocyte count serves as a useful screen for hemolysis or blood loss. Testing for specific causes of the anemia is performed. Occasionally, examination of the bone marrow is required for diagnosis. Molecular testing is increasingly being use to aid the diagnostic process. This article reviews diagnostic tests for anemia and suggests a rational approach to determining the etiology of a patient's anemia.

  13. Treatment of autoimmune hemolytic anemias.

    PubMed

    Zanella, Alberto; Barcellini, Wilma

    2014-10-01

    Autoimmune hemolytic anemia (AIHA) is a relatively uncommon disorder caused by autoantibodies directed against self red blood cells. It can be idiopathic or secondary, and classified as warm, cold (cold hemagglutinin disease (CAD) and paroxysmal cold hemoglobinuria) or mixed, according to the thermal range of the autoantibody. AIHA may develop gradually, or have a fulminant onset with life-threatening anemia. The treatment of AIHA is still not evidence-based. The first-line therapy for warm AIHA are corticosteroids, which are effective in 70-85% of patients and should be slowly tapered over a time period of 6-12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20%), rituximab (effective in approx. 80-90% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option. As the experience with rituximab evolves, it is likely that this drug will be located at an earlier point in therapy of warm AIHA, before more toxic immunosuppressants, and in place of splenectomy in some cases. In CAD, rituximab is now recommended as first-line treatment.

  14. Anemia in pediatric renal transplant recipients.

    PubMed

    Kausman, Joshua Yehuda; Powell, Harley Robert; Jones, Colin Lindsay

    2004-05-01

    The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses

  15. How Is Anemia Diagnosed?

    MedlinePlus

    ... parts of your blood. The test checks your hemoglobin and hematocrit (hee-MAT-oh-crit) levels. Hemoglobin is the iron-rich protein in red blood ... up in your blood. A low level of hemoglobin or hematocrit is a sign of anemia. The ...

  16. Anemia and School Participation

    ERIC Educational Resources Information Center

    Bobonis, Gustavo J.; Miguel, Edward; Puri-Sharma, Charu

    2006-01-01

    Anemia is among the most widespread health problems for children in developing countries. This paper evaluates the impact of a randomized health intervention delivering iron supplementation and deworming drugs to Indian preschool children. At baseline, 69 percent were anemic and 30 percent had intestinal worm infections. Weight increased among…

  17. Sickle Cell Anemia Bibliography.

    ERIC Educational Resources Information Center

    Christy, Steven C.

    Presents sources for the acquisition of medical, social, psychological, educational, and practical knowledge of sickle cell anemia. The materials listed are designed to help parents, educators, and public service workers. Materials include journal articles, films, brochures, slides, and fact sheets. The usual bibliographic information is given.…

  18. Autoimmune Hemolytic Anemia.

    PubMed

    Liebman, Howard A; Weitz, Ilene C

    2017-03-01

    Autoimmune hemolytic anemia is an acquired autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens causing shortened erythrocyte survival. The disorders can present as a primary disorder (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immune modulation with corticosteroids and other agents.

  19. How to approach chronic anemia.

    PubMed

    Koury, Mark J; Rhodes, Melissa

    2012-01-01

    We present herein an approach to diagnosing the cause of chronic anemia based on a patient's history and complete blood cell count (CBC). Four patterns that are encountered frequently in CBCs associated with chronic anemias are considered: (1) anemia with abnormal platelet and/or leukocyte counts, (2) anemia with increased reticulocyte counts, (3) life-long history of chronic anemia, and (4) anemia with inappropriately low reticulocytes. The pathophysiologic bases for some chronic anemias with low reticulocyte production are reviewed in terms of the bone marrow (BM) events that reduce normal rates of erythropoiesis. These events include: apoptosis of erythroid progenitor and precursor cells by intrinsic and extrinsic factors, development of macrocytosis when erythroblast DNA replication is impaired, and development of microcytosis due to heme-regulated eIF2α kinase inhibition of protein synthesis in iron-deficient or thalassemic erythroblasts.

  20. Anemia in heart failure: pathophysiologic insights and treatment options.

    PubMed

    Terrovitis, John V; Anastasiou-Nana, Maria; Kaldara, Elissavet; Drakos, Stavros G; Nanas, Serafeim N; Nanas, John N

    2009-01-01

    Anemia has been recognized as a very common and serious comorbidity in heart failure, with a prevalence ranging from 10 to 79%, depending on diagnostic definition, disease severity and patient characteristics. A clear association of anemia with worse prognosis has been confirmed in multiple heart failure trials. This finding has recently triggered intense scrutiny in order to identify the underlying pathophysiology and the best treatment options. Etiology is multifactorial, with iron deficiency and cytokine activation (anemia of chronic disease) playing the most important roles. Treatment is aimed at not only restoring hemoglobin values back to normal, but also at improving the patient's symptoms, functional capacity and hopefully the outcome. Iron supplementation and erythropoietin-stimulating agents have been used for this purpose, either alone or in combination. In this review, the recent advances in elucidating the mechanisms leading to anemia in the setting of heart failure are presented and the evidence supporting the use of different treatment approaches are discussed.

  1. Sickle Cell Disease (For Parents)

    MedlinePlus

    ... from each parent has hemoglobin SS disease , also called sickle cell anemia . A person can also inherit a sickle cell ... Is Affected? In the United States, hemoglobin SS disease (sickle cell anemia) affects mostly African Americans. However, forms of sickle ...

  2. [Hereditary sideroblastic anemia: a rare diagnosis].

    PubMed

    Brahem-Jmili, N; Salem, N; Abdelkefi, S; Champ, B Grand; Bekri, S; Sboui, H; Mahjoub, T; Yacoub, S; Kortas, M

    2004-01-01

    Hereditary sideroblastic anemia is a very rare disease recessive and X-linked that affect heme biosynthesis by deficit or decreased of delta aminolevulinic acid synthase (ALAS) activity. We report a case of a six-month-old boy, admitted in the hospital for anemic syndrome. The hemogram showed anemia (hemoglobin: 4.5 g/dL), frankly hypochronic microcytic and a regenerated (mean corpuscular hemoglobin concentration: 26 g/dL, mean cell volume: 53 fl, reticulocytes: 10 x 10(9)/L) with red cells morphologic disorders in smears (anisopoikylocytosis) without attack of the other lineages; white blood cells: 11 x 10(9)/L (neutrophils: 64% and lymphocytes: 35%); platelets: 350 x 10(9)/L. Examination of bone marrow showed an important erythroid hyperplasia (about 69%) with dyserythropoiesis. Perls stain revealed intense siderosis with 90% of ringed sideroblasts and a large number of siderocytes. Exploration of ALAS2 and ABC7 genes on the DNA of the infant was not found abnormalities. Treatment with pyridoxine corrects moderately the anemia. By the way, we proposed to remind that iron deficiency, inflammatory syndrome and thalassemia are the common microcytic anemia. However, it's mandatory to explore other causes if diagnosis is not solved.

  3. Living with Diamond Blackfan anemia: a challenge toward survival.

    PubMed

    Brannan, Sandy

    2004-01-01

    As the world of medicine and nursing advance, children with once terminal childhood diseases are now surviving into young adulthood. Nurses must learn to care for pediatric patients who transition to adulthood. This article explores Diamond Blackfan Anemia, once considered a terminal childhood disease that can now be a disease of young adulthood.

  4. Anemia and Microvascular Complications in Patients With Type 2 Diabetes Mellitus

    PubMed Central

    Hosseini, Mahboobeh Sadat; Rostami, Zohreh; Saadat, Alireza; Saadatmand, Sayyed Mehdi; Naeimi, Effat

    2014-01-01

    Background: Although chronic kidney disease-induced anemia is more prevalent in patients with diabetes mellitus (DM), anemia is a common finding prior to manifestation of kidney disease. In presence of some risk factors at the time of diagnosing DM, microvascular complications must be considered. The effect of anemia as a risk factor on progression of DM complications is still unclear. Objectives: The aim of the study was to determine the prevalence of anemia and its association with microvascular complications in patients with type 2 DM. Patients and Methods: This cross-sectional study was performed in the outpatient endocrinology clinic at Baqiyatallah University of Medical Sciences Hospital, Tehran, Iran. Study was done from February 2011 to February 2012. Patients with type 2 DM without any obvious symptom or sign of anemia were included in study. Results: A total of 93 patients (30.4%) had anemia including 46 (15.1%) with normochromic normocytic, 44 (14.4%) with hyperchromic microcytic, and 3 (1%) with hyperchromic macrocytic anemias. There was a positive correlation between duration of DM and anemia. Microvascular complications were more frequent with normocytic or microcytic anemias. Glomerular filtration rate (GFR) was higher in patients without anemia; moreover, nephropathy was less frequent among them. Among patients with anemia, 43% had GFR of more than 90 mL/min and 19.4% had normoalbuminuria. Neuropathy, nephropathy, and retinopathy had strong association with anemia (odds ratio of 1.99, 1.7, and 1.5, respectively). Conclusions: Anemia is a common complication of DM and is associated with duration of disease and microvascular complications. PMID:25695026

  5. Two-trait-locus linkage analysis: A powerful strategy for mapping complex genetic traits

    SciTech Connect

    Schork, N.J.; Boehnke, M. ); Terwilliger, J.D.; Ott, J. )

    1993-11-01

    Nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, the authors explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. The authors compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. The authors also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one-marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, the authors also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that the authors consider, the authors find that two-trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one-trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, the authors also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. The authors discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models. 37 refs., 1 fig., 4 tabs.

  6. Anemia as the Main Manifestation of Myelodysplastic Syndromes.

    PubMed

    Santini, Valeria

    2015-10-01

    Myelodysplastic syndromes (MDS) are a constellation of different diseases sharing anemia in the great majority of cases, and this cytopenia defines these pathologies and their most dramatic clinical manifestations. Anemia in MDS is due to ineffective erythropoiesis, with a high degree of apoptosis of marrow erythroid progenitors. These progenitors show distinctive dysplastic features that consent diagnosis, and are recognizable and differentiated, although not easily, from other morphologic alterations present in other types of anemia. Reaching the diagnosis of MDS in a macrocytic anemia and alleviating the symptoms of anemia are therefore an essential objective of the treating physician. In this work, the signs and symptoms of anemia in MDS, as well as its peculiar pathophysiology, are discussed. Erythopoietic stimulating agents (ESAs) are providing the best treatment for anemic MDS patients, but their use is still not approved by health agencies. While still waiting for this waiver, their clinical use is widespread and their effectivness is well known, as well as the dismal prognosis of patients who do not respond to ESAs and require transfusions. MDS with del5q constitute a unique model of anemia whose complex pathophysiology has been clarified at least partially, defining its link to ribosomal alterations likewise what observed in hereditary anemias like Blackfan Diamond anemia. Lenalidomide is the agent that has shown striking and specific erythropoietic activity in del5q MDS, and the basis of this response is starting to be understood. Several new agents are under evaluation for ESA refractory/relapsed MDS patients, targeting different putative mechanisms of ineffective erythropoiesis, and are here reviewed.

  7. Relation between blood lead levels and childhood anemia in India.

    PubMed

    Jain, Nitin B; Laden, Francine; Guller, Ulrich; Shankar, Anoop; Kazani, Shamsah; Garshick, Eric

    2005-05-15

    Lead pollution is a substantial problem in developing countries such as India. The US Centers for Disease Control and Prevention has defined an elevated blood lead level in children as > or = 10 microg/dl, on the basis of neurologic toxicity. The US Environmental Protection Agency suggests a threshold lead level of 20-40 microg/dl for risk of childhood anemia, but there is little information relating lead levels <40 microg/dl to anemia. Therefore, the authors examined the association between lead levels as low as 10 mug/dl and anemia in Indian children under 3 years of age. Anemia was divided into categories of mild (hemoglobin level 10-10.9 g/dl), moderate (hemoglobin level 8-9.9 g/dl), and severe (hemoglobin level <8 g/dl). Lead levels <10 mug/dl were detected in 568 children (53%), whereas 413 (38%) had lead levels > or = 10-19.9 microg/dl and 97 (9%) had levels > or = 20 microg/dl. After adjustment for child's age, duration of breastfeeding, standard of living, parent's education, father's occupation, maternal anemia, and number of children in the immediate family, children with lead levels > or = 10 microg/dl were 1.3 (95% confidence interval: 1.0, 1.7) times as likely to have moderate anemia as children with lead levels <10 microg/dl. Similarly, the odds ratio for severe anemia was 1.7 (95% confidence interval: 1.1, 2.6). Health agencies in India should note the association of elevated blood lead levels with anemia and make further efforts to curb lead pollution and childhood anemia.

  8. [Anemia in the elderly].

    PubMed

    Maerevoet, M; Sattar, L; Bron, D; Gulbis, B; Pepersack, T

    2014-09-01

    Anaemia is a problem that affects almost 10% over 65 years and 20% over 85 years. There is no physiological anaemia in the elderly. Any anaemia expresses the existence of a pathological process, regardless of its severity. Anaemia in the elderly is always associated with a poor prognosis that is in terms of mortality, morbidity and risk of fragility. The diagnostic approach to anemia in the elderly is the same as in younger individual. There are many causes of anaemia; anaemia balance is a complex diagnostic process. Most anaemias are due to a deficiency, chronic inflammation or comorbidity. However, in the elderly, the etiology of anaemia is often multifactorial. In a number of cases remain unexplained anaemia. In a number of cases, anemia remain unexplained. Treatment of anaemia is the treatment of the cause, but specific therapeutic aspects to the elderly should be considered, as among other martial substitution or use of erythropoietin (EPO).

  9. Hereditary sideroblastic anemia with associated platelet abnormalities.

    PubMed

    Soslau, G; Brodsky, I

    1989-12-01

    A 62 year old male (R.H.) presented with a mild anemia (Hb 11-12 gm%) and a history of multiple hemorrhagic episodes. The marrow had 40-50% sideroblasts. Marrow chromosomes were normal. His wife was hematologically normal, while one daughter, age 30 years, had a sideroblastic anemia (Hb 11-12 gm%) with 40-50% sideroblasts in the marrow. Her anemia was first noted at age 15 years. Administration of vitamin B6 did not correct the anemia in either the father or daughter. Platelet abnormalities inherited jointly with this disorder are described for the first time. Both R.H. and his daughter had prolonged bleeding times, with normal PTT, PT times, fVIII:C, fVIII:Ag levels, and vWF multimers, which may rule out a von Willebrand's disease. They have normal platelet numbers but abnormally low platelet adhesiveness and greatly depressed ADP, collagen, and epinephrine responsiveness. Response to ristocetin was in the low normal range, and aggregation with thrombin was normal. While desmopressin completely normalized R.H.'s bleeding time, none of these platelet parameters were improved. No differences in the SDS PAGE protein patterns of RH platelets could be detected in comparison to normal samples. His platelets took up and released serotonin (5HT) normally, and electron micrographs defined no morphological abnormalities. However, no ATP was released from platelets activated with collagen, and when followed by thrombin about fourfold greater ATP was released by control platelets as compared to RH platelets. The dense granule fraction derived from RH platelets contained about 20% the level of ATP, 40% the level of ADP, and 50% the level of 5HT detected in a normal sample. The results indicate that the bleeding disorder is related to a non-classical heritable storage pool defect. The connection between the inherited sideroblastic anemia and platelet defects is obscure.

  10. Anemia: a cause of intolerance to thyroxine sodium.

    PubMed

    Shakir, K M; Turton, D; Aprill, B S; Drake, A J; Eisold, J F

    2000-02-01

    Usual causes of intolerance to thyroxine sodium include coronary artery disease, advanced age, untreated adrenal insufficiency, and severe hypothyroidism. We describe 4 patients with iron deficiency anemia and primary hypothyroidism. After treatment with thyroxine sodium, these patients developed palpitations and feelings of restlessness, which necessitated discontinuation of the thyroid hormone. After the anemia was treated with ferrous sulfate for 4 to 7 weeks, they were able to tolerate thyroxine sodium therapy. Iron deficiency anemia coexisting with primary hypothyroidism results in a hyperadrenergic state. In such patients, we postulate that thyroid hormone administration causes palpitations, nervousness, and feelings of restlessness. Correction of any existing pronounced anemia in hypothyroid patients who are intolerant to thyroxine sodium therapy may result in tolerance to this agent.

  11. Refractory anemia in human immunodeficiency virus: Expect the unexpected.

    PubMed

    Mirgh, Sumeet Prakash; Mishra, Vikas A; Shah, Virti D; Sorabjee, Jehangir Soli

    2016-01-01

    Pure red cell aplasia (PRCA) is an uncommon hematological disorder affecting selectively the erythroid cell lines. PRCA is defined as anemia with normal leukocyte and platelet counts, a corrected reticulocyte count <1%, <5% erythroid precursors in the bone marrow and an absence of hemolysis. We describe a case of Zidovudine (AZT) induced PRCA causing severe anemia in a patient taking antiretroviral therapy (ART) after 4 months of starting therapy and in whom all other causes were excluded. The hematological abnormalities resolved after AZT was replaced with tenofovir and the patient remained transfusion independent thereafter. A slowly progressive normocytic-normochromic anemia and reticulocytopenia, without leukopenia and thrombocytopenia in a patient, should raise the suspicion of PRCA. Search for underlying diseases, infections and drugs may help in the diagnosis and etiology of acquired PRCA. Elimination of potentially causative factors may induce complete recovery. AZT is a well-known cause of anemia and thus should be used with caution in the initiation of ART.

  12. Anemia associated with chronic heart failure: current concepts.

    PubMed

    Shah, Ravish; Agarwal, Anil K

    2013-01-01

    Anemia is a frequent comorbidity of heart failure and is associated with poor outcomes. Anemia in heart failure is considered to develop due to a complex interaction of iron deficiency, kidney disease, and cytokine production, although micronutrient insufficiency and blood loss may contribute. Currently, treatment of anemia of heart failure lacks clear targets and specific therapy is not defined. Intravenous iron use has been shown to benefit anemic as well as nonanemic patients with heart failure. Treatment with erythropoietin-stimulating agents has been considered alone or in combination with iron, but robust evidence to dictate clear guidelines is not currently available. Available and emerging new agents in the treatment of anemia of heart failure will need to be tested in randomized, controlled studies.

  13. [Nutritional anemias in elderly patients].

    PubMed

    Serraj, Khalid; Federici, Laure; Kaltenbach, Georges; Andrès, Emmanuel

    2008-09-01

    Nutritional deficiencies cause one third of the cases of anemia in the elderly. The urgency of anemia management in elderly patients depends on tolerance and repercussions, rather than only on the hemoglobin level. Iron, vitamin B12 and folate are the most common deficiencies, and their levels should be tested. Chronic gastrointestinal bleeding is the principal cause of iron-deficiency anemia. Management is based on supplementation combined with effective etiological treatment.

  14. Genetics Home Reference: Diamond-Blackfan anemia

    MedlinePlus

    ... Understand Genetics Home Health Conditions Diamond-Blackfan anemia Diamond-Blackfan anemia Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Diamond-Blackfan anemia is a disorder of the bone ...

  15. Iron-Deficiency Anemia (For Parents)

    MedlinePlus

    ... Blood Breastfeeding FAQs: How Much and How Often Vegan Food Guide Vegetarianism Anemia Word! Anemia Vitamins About ... Vegetarian Blood Coping With Common Period Problems Anemia Vegan Food Guide Vitamins and Minerals Contact Us Print ...

  16. Iron-Deficiency Anemia (For Parents)

    MedlinePlus

    ... Your 1- to 2-Year-Old Iron-Deficiency Anemia KidsHealth > For Parents > Iron-Deficiency Anemia Print A ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  17. The IGF2 Locus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin-like growth factor 2 (IGF2) is a peptide hormone regulating various cellular processes such as proliferation and apoptosis. IGF2 is vital to embryo development. The IGF2 locus covers approximately 150-kb genomic region on human chromosome 11, containing two imprinted genes, IGF2 and H19, sha...

  18. [Iron deficiency anemia and anemia of chronic disorders].

    PubMed

    Metzgeroth, G; Hastka, J

    2015-09-01

    Hypochromic-microcytic anemias are characterized by a hemoglobin deficiency of the erythrocytes. The main reason for the insufficient hemoglobin synthesis is, with exception of thalassemia and a few other rare conditions, primarily a disorder of iron metabolism. Differential diagnostic considerations are focused on iron deficiency anemia, with approximately 80% the most common form of anemia worldwide. Iron deficiency anemia shows a particularly high prevalence in developing countries, but is also in industrialized Western countries the most common cause of anemia. Infants, toddlers, premenopausal or pregnant women, and elderly people are at particularly high risk of iron deficiency anemia. The most important differential diagnosis for iron deficiency anemia is the anemia of chronic disorders (ACD). This anemia is caused by a disturbance of iron utilization (functional iron deficiency), in which iron absorption and iron release, as a nonspecific defense mechanism, is blocked to restrict iron availability for the inflammatory process but also withhold iron from the erythropoiesis. ACD is not rare, but plays a significant role in hospitalized patients and in the elderly. The differentiation between ACD and iron deficiency anemia is highly important from a clinical point of view, due to different types of further management. The cause for iron deficiency should be clarified in each case, whereas the etiology for ACD is often obvious. The standard treatment of iron deficiency anemia is oral iron supplementation. Intravenous iron application is reserved for problem patients. The best treatment for ACD is the elimination of the underlying chronic disorder. In case of persistent ACD, red blood cell transfusions, erythropoietin, and intravenous iron are used therapeutically.

  19. Physical mapping of the major early-onset familial Alzheimer`s disease locus on chromosome 14 and analysis of candidate gene sequences

    SciTech Connect

    Tanzi, R.E.; Romano, D.M.; Crowley, A.C.

    1994-09-01

    Genetic studies of kindreds displaying evidence for familial AD (FAD) have led to the localization of gene defects responsible for this disorder on chromosomes 14, 19, and 21. A minor early-onset FAD gene on chromosome 21 has been identified to enode the amyloid precursor protein (APP), and the late-onset FAD susceptibility locus on chromosome 19 has been shown to be in linkage disequilibrium with the E4 allele of the APOE gene. Meanwhile, the locus responsible for the major form of early-onset FAD on chromosome 14q24 has not yet been identified. By recombinational analysis, we have refined the minimal candidate region containing the gene defect to approximately 3 megabases in 14q24. We will describe our laboratory`s progress on attempts to finely localize this locus, as well as test known candidate genes from this region for either inclusion in the minimal candidate region or the presence of pathogenic mutations. Candidate genes that have been tested so far include cFOS, heat shock protein 70 member (HSF2A), transforming growth factor beta (TGFB3), the trifunctional protein C1-THF synthase (MTHFD), bradykinin receptor (BR), and the E2k component of a-ketoglutarate dehydrogenase. HSP2A, E2k, MTHFD, and BR do not map to the current defined minimal candidate region; however, sequence analysis must be performed to confirm exclusion of these genes as true candidates. Meanwhile, no pathogenic mutations have yet been found in cFOS or TGFB3. We have also isolated a large number of novel transcribed sequences from the minimal candidate region in the form of {open_quotes}trapped exons{close_quotes} from cosmids identified by hybridization to select YAC clones; we are currently in the process of searching for pathogenic mutations in these exons in affected individuals from FAD families.

  20. [Diagnosis and treatment of hemolytic anemia].

    PubMed

    Kamesaki, Toyomi

    2015-10-01

    Hemolytic anemia is defined as anemia due to a reduction of the RBC lifespan to less than the normal range of approximately 120 days. Patients with anemia and jaundice are often suspected to have hemolysis. Herein, different causes of hemolysis and the diagnostic algorithm are reviewed. Currently, there is no generic treatment for hemolytic anemia. Appropriate management of a patient with hemolytic anemia requires determination of the underlying cause. Treatments for the different causes of hemolytic anemia are also reviewed.

  1. Incidence of anemia in older Koreans: community-based cohort study.

    PubMed

    Choi, Chul Won; Lee, Juneyoung; Park, Kyong Hwa; Choi, In Keun; Kim, Seok Jin; Seo, Jae Hong; Kim, Byung Soo; Shin, Sang Won; Kim, Yeul Hong; Kim, Jun Suk

    2005-01-01

    Most epidemiologic data are related to the prevalence of anemia, and there is little information regarding the incidence or etiology of newly diagnosed anemia in older people. The purpose of this study was to define the incidence and characteristics of anemia in the elderly population of Korea. Three hundred thirty-two independent, community-living, elderly persons aged 60 years and older were enrolled, and laboratory tests including iron profiles were performed. The mean age was 72+/-4.8 years and the mean hemoglobin was 13.4+/-1.1g/dl. During the follow-up period of 3 years, 24 subjects (3 males and 21 females) were newly diagnosed with anemia, which led to a 3-year incidence of 7.2% (24/332). Among the 24 subjects with new-onset anemia, iron deficiency anemia (IDA) was diagnosed in 5 subjects, while anemia of chronic disease (ACD) was detected in 8 subjects. Underlying illnesses were diabetes mellitus, osteoarthritis, renal insufficiency, hypothyroidism and malignancy. In those subjects with new-onset anemia, the serum iron, ferritin, transferrin saturation and albumin were lower than in the normal group. In conclusion, the 3-year incidence of anemia among Korean elderly people was determined to be 7.2%, and ACD was the most commonly defined cause of anemia.

  2. Iron Deficiency and Other Types of Anemia in Infants and Children.

    PubMed

    Wang, Mary

    2016-02-15

    Anemia, defined as a hemoglobin level two standard deviations below the mean for age, is prevalent in infants and children worldwide. The evaluation of a child with anemia should begin with a thorough history and risk assessment. Characterizing the anemia as microcytic, normocytic, or macrocytic based on the mean corpuscular volume will aid in the workup and management. Microcytic anemia due to iron deficiency is the most common type of anemia in children. The American Academy of Pediatrics and the World Health Organization recommend routine screening for anemia at 12 months of age; the U.S. Preventive Services Task Force found insufficient evidence to assess the benefits vs. harms of screening. Iron deficiency anemia, which can be associated with cognitive issues, is prevented and treated with iron supplements or increased intake of dietary iron. The U.S. Preventive Services Task Force found insufficient evidence to recommend screening or treating pregnant women for iron deficiency anemia to improve maternal or neonatal outcomes. Delayed cord clamping can improve iron status in infancy, especially for at-risk populations, such as those who are preterm or small for gestational age. Normocytic anemia may be caused by congenital membranopathies, hemoglobinopathies, enzymopathies, metabolic defects, and immune-mediated destruction. An initial reticulocyte count is needed to determine bone marrow function. Macrocytic anemia, which is uncommon in children, warrants subsequent evaluation for vitamin B12 and folate deficiencies, hypothyroidism, hepatic disease, and bone marrow disorders.

  3. Anemia in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Barbieri, Jéssica; Fontela, Paula Caitano; Winkelmann, Eliane Roseli; Zimmermann, Carine Eloise Prestes; Sandri, Yana Picinin; Mallet, Emanelle Kerber Viera; Frizzo, Matias Nunes

    2015-01-01

    The objective of this study was to evaluate the prevalence of anemia in DM2 patients and its correlation with demographic and lifestyle and laboratory variables. This is a descriptive and analytical study of the type of case studies in the urban area of the Ijuí city, registered in programs of the Family Health Strategy, with a total sample of 146 patients with DM2. A semistructured questionnaire with sociodemographic and clinical variables and performed biochemical test was applied. Of the DM2 patients studied, 50 patients had anemia, and it was found that the body mass items and hypertension and hematological variables are significantly associated with anemia of chronic disease. So, the prevalence of anemia is high in patients with DM2. The set of observed changes characterizes the anemia of chronic disease, which affects quality of life of diabetic patients and is associated with disease progression, development, and comorbidities that contribute significantly to increasing the risk of cardiovascular diseases. PMID:26640706

  4. Renal failure in sickle cell anemia.

    PubMed

    Wong, W Y; Elliott-Mills, D; Powars, D

    1996-12-01

    ESRD is a major complication in young adults with sickle cell anemia. As more patients with sickle cell anemia reach the third and fourth decades of life, the incidence of clinically apparent renal insufficiency will increase. As we understand the pathophysiology of renal damage and the effects of various therapies on the sickle renal vasculature, we can tailor specific management without further compromising already impaired renal function. Diagnostic clues must be recognized prior to the onset of irreversible damage, with appropriate intervention initiated at each age group. Bone marrow transplantation (BMT) is the only available cure for SCA at the present time. The demonstration that several distinct haplotypes of the beta s gene cluster on chromosome 11 influence the clinical expression of sickle cell anemia may be useful in delineating children who are at high risk for severe disease, and hence candidates for such hazardous therapeutic interventions as BMT prior to onset of clinically discernable disease. Current BMT preparative regimens can produce renal cortical and pulmonary toxicity, posing a patient selection problem in those cases in which the vasculopathy of the major organs is at an early stage and might be potentially repairable. Gene therapy without toxic preparative regimens is the ultimate answer. The challenge for the near future is the development of effective early therapeutic intervention during childhood and young adulthood.

  5. Management of anemia by convective treatments.

    PubMed

    Locatelli, Francesco; Manzoni, Celestina; Del Vecchio, Lucia; Di Filippo, Salvatore; Pontoriero, Giuseppe; Cavalli, Andrea

    2011-01-01

    Anemia secondary to chronic kidney disease is a complex syndrome. Adequate dialysis can contribute to its correction by removing small and possibly medium/large molecules that may inhibit erythropoiesis. A clear relationship among hemoglobin, erythropoiesis stimulating agent (ESA) dose and increase in dialysis dose has been pointed out by a number of prospective and retrospective studies. Increasing attention has also been paid to the relationship between dialysis, increased inflammatory stimulus and ESA response, as dialysate contamination and low compatible treatments may increase cytokine production and consequently inhibit erythropoiesis. As medium/large molecular weight inhibitors can be removed only by more permeable membranes, convective treatment sand, particularly, online treatments, could theoretically improve anemia correction by two mechanisms: higher removal of medium and large solutes (possibly containing bone marrow inhibitors) and reduced microbiological and pyrogenic contamination of the dialysate. Unfortunately, available results are conflicting. Large, prospective, randomized studies on this topic are still needed.

  6. Iron overload complicating sideroblastic anemia--is the gene for hemochromatosis responsible?

    PubMed

    Barron, R; Grace, N D; Sherwood, G; Powell, L W

    1989-04-01

    Idiopathic hemochromatosis is a hereditary disease that is associated with human leucocytic antigens A3, B7, and B14. A genetic association between human leucocytic antigen-linked hemochromatosis and idiopathic refractory sideroblastic anemia has been suggested that may predispose some patients with idiopathic refractory sideroblastic anemia to develop gross iron overload. Study of the family of a patient with idiopathic refractory sideroblastic anemia and hemochromatosis revealed that 2 of 5 first-degree relatives had significant elevations of serum ferritin, and a shared human leucocytic antigen haplotype, supporting the concept that patients with idiopathic refractory sideroblastic anemia and significant iron overload have at least one allele for hemochromatosis.

  7. Plasma hepcidin levels and anemia in old age. The Leiden 85-Plus Study.

    PubMed

    den Elzen, Wendy P J; de Craen, Anton J M; Wiegerinck, Erwin T; Westendorp, Rudi G J; Swinkels, Dorine W; Gussekloo, Jacobijn

    2013-03-01

    Hepcidin, an important regulator of iron homeostasis, is suggested to be causally related to anemia of inflammation. The aim of this study was to explore the role of plasma hepcidin in anemia among older persons from the general population. The Leiden 85-Plus Study is a population-based study of 85-year olds in Leiden, the Netherlands. Eighty-five-year old inhabitants of Leiden were enrolled between September 1997 and September 1999. At the age of 86, plasma hepcidin was determined with time of flight mass spectrometry in 490 participants [160 (32.7%) male, 114 (23.3%) with anemia]. Anemia was defined according to criteria of the World Health Organization (hemoglobin level <13 g/dL for men and hemoglobin <12 g/dL for women). The median plasma hepcidin level was 3.0 nM [interquartile range (IQR) 1.8-4.9]. We found strong correlations between plasma hepcidin and body iron status, C-reactive protein and erythropoietin levels. Significantly higher hepcidin levels were found in participants with anemia of inflammation (P<0.01), in participants with anemia of kidney disease (P=0.01), and in participants with unexplained anemia (P=0.01) than in participants without anemia. Participants with iron-deficiency anemia had significantly lower plasma hepcidin levels than participants without anemia (P<0.01). In conclusion, older persons with anemia of inflammation have higher hepcidin levels than their counterparts without anemia. The potential clinical value of hepcidin in future diagnostic algorithms for anemia has to be explored.

  8. Effects of Oral L-Carnitine Supplementation on Lipid Profile, Anemia, and Quality of Life in Chronic Renal Disease Patients under Hemodialysis: A Randomized, Double-Blinded, Placebo-Controlled Trial

    PubMed Central

    Emami Naini, Afsoon; Moradi, Mahnaz; Mortazavi, Mojgan; Amini Harandi, Asghar; Hadizadeh, Mehdi; Shirani, Farhad; Basir Ghafoori, Hamed; Emami Naini, Pardis

    2012-01-01

    In patients on maintenance hemodialysis several factors reduce the body stored carnitine which could lead to dyslipidemia, anemia, and general health in these patients. We evaluated the effect of oral L-carnitine supplementation on lipid profiles, anemia, and quality of life (QOL) in hemodialysis patients. In a randomized, double-blinded, placebo-controlled trial, end-stage renal disease (ESRD) patients on hemodialysis received either L-carnitine 1 g/d (n = 24) or placebo (27 patients) for 16 weeks. At the end of the study, there was a significant decrease in triglyceride (−31.1 ± 38.7 mg/dL, P = 0.001) and a significant increase in HDL (3.7 ± 2.8 mg/dL, P < 0.001) levels in the carnitine group. Decrease in total cholesterol (−6.6 ± 16.0 mg/dL, P = 0.075) and increase in hemoglobin (0.7 ± 1.7 g/dL, P = 0.081) concentrations in the carnitine group were not significant. There was no statistically significant changes in LDL in any group (P > 0.05). Erythropoietin dose was significantly decreased in both the carnitine (−4750 ± 5772 mg, P = 0.001) and the placebo group (−2000 ± 4296 mg, P < 0.05). No improvement was observed in QOL scores of two groups. In ESRD patients under maintenance hemodialysis, oral L-carnitine supplementation may reduce triglyceride and cholesterol and increase HDL and hemoglobin and subsequently reduce needed erythropoietin dose without effect on QOL. PMID:22720143

  9. [Anemia and iron deficiency in the elderly. Prevalence, diagnostics and new therapeutic options].

    PubMed

    Röhrig, G; Doehner, W; Schaefer, R M; Schulz, R J

    2012-04-01

    The prevalence of anemia in geriatric patients is high. With some variation in different patient cohorts, prevalence of anemia can reach 40%. Anemia is not an age-related disease on its own, but is a symptom with multifactorial genesis and high risk potential. It directly influences mortality, morbidity, and the rate of hospitalization, particularly in older patients suffering from chronic heart failure or chronic kidney disease. The high prevalence of anemia in chronic kidney disease is explained by a combination of erythropoietin and iron deficiency. This review summarizes the recommendations of the iron symposium at the 2010 German Geriatric Society Meeting in Potsdam, Germany. It intends to provide current information on prevalence, diagnostic work-up, and therapeutic options for anemia in the rapidly growing group of elderly patients.

  10. Prevention of Iron-Deficiency Anemia in Infants and Children of Preschool Age.

    ERIC Educational Resources Information Center

    Fomon, Samuel J.

    Iron-deficiency anemia is almost certainly the most prevalent nutritional disorder among infants and young children in the United States. Anemia is frequently seen among children of low socioeconomic status but is probably also the most frequent nutritional deficiency disease seen among children cared for by private doctors. Possible reasons for…

  11. A Case of Fetal Intestinal Volvulus Without Malrotation Causing Severe Anemia

    PubMed Central

    Nakagawa, Tomoko; Tachibana, Daisuke; Kitada, Kohei; Kurihara, Yasushi; Terada, Hiroyuki; Koyama, Masayasu; Sakae, Yukari; Morotomi, Yoshiki; Nomura, Shiho; Saito, Mika

    2015-01-01

    Fetal intestinal volvulus without malrotation is a rare, life-threatening disease. Left untreated, hemorrhage from necrotic bowel tissue will lead to severe fetal anemia and even intrauterine death. We encountered a case of fetal intestinal volvulus causing severe anemia, which was diagnosed postnatally and successfully treated with surgical intervention. PMID:25628516

  12. How I treat autoimmune hemolytic anemias in adults.

    PubMed

    Lechner, Klaus; Jäger, Ulrich

    2010-09-16

    Autoimmune hemolytic anemia is a heterogeneous disease with respect to the type of the antibody involved and the absence or presence of an underlying condition. Treatment decisions should be based on careful diagnostic evaluation. Primary warm antibody autoimmune hemolytic anemias respond well to steroids, but most patients remain steroid-dependent, and many require second-line treatment. Currently, splenectomy can be regarded as the most effective and best-evaluated second-line therapy, but there are still only limited data on long-term efficacy and adverse effects. The monoclonal anti-CD20 antibody rituximab is another second-line therapy with documented short-term efficacy, but there is limited information on long-term efficacy and side effects. The efficacy of immunosuppressants is poorly evaluated. Primary cold antibody autoimmune hemolytic anemias respond well to rituximab but are resistant to steroids and splenectomy. The most common causes of secondary autoimmune hemolytic anemias are malignancies, immune diseases, or drugs. They may be treated in a way similar to primary autoimmune hemolytic anemias, by immunosuppressants or by treatment of the underlying disease.

  13. Erythro-megakaryocytic transcription factors associated with hereditary anemia.

    PubMed

    Crispino, John D; Weiss, Mitchell J

    2014-05-15

    Most heritable anemias are caused by mutations in genes encoding globins, red blood cell (RBC) membrane proteins, or enzymes in the glycolytic and hexose monophosphate shunt pathways. A less common class of genetic anemia is caused by mutations that alter the functions of erythroid transcription factors (TFs). Many TF mutations associated with heritable anemia cause truncations or amino acid substitutions, resulting in the production of functionally altered proteins. Characterization of these mutant proteins has provided insights into mechanisms of gene expression, hematopoietic development, and human disease. Mutations within promoter or enhancer regions that disrupt TF binding to essential erythroid genes also cause anemia and heritable variations in RBC traits, such as fetal hemoglobin content. Defining the latter may have important clinical implications for de-repressing fetal hemoglobin synthesis to treat sickle cell anemia and β thalassemia. Functionally important alterations in genes encoding TFs or their cognate cis elements are likely to occur more frequently than currently appreciated, a hypothesis that will soon be tested through ongoing genome-wide association studies and the rapidly expanding use of global genome sequencing for human diagnostics. Findings obtained through such studies of RBCs and associated diseases are likely generalizable to many human diseases and quantitative traits.

  14. Selective intestinal malabsorption of vitamin B12 displays recessive Mendelian inheritance: Assignment of a locus to chromosome 10 by linkage

    SciTech Connect

    Aminoff, M.; Tahvanainen, E.; Chapelle, A. de la

    1995-10-01

    Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal recessive inheritance. It appears to have a worldwide distribution, and comparatively high incidences were reported 30 years ago in Finland and Norway. More recently, the Mendelian inheritance of the condition has been questioned because almost no new cases have occurred in these populations. Here we report linkage studies assigning a recessive-gene locus for the disease to chromosome 10 in previously diagnosed multiplex families from Finland and Norway, proving the Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM interval between markers D10S548 and D10S466, with a multipoint maximum lod score (Z{sub max}) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in these families did not appear to constitute any examples of nonpenetrance. We hypothesize that the paucity of new cases in these populations is due either to a dietary effect on the gene penetrance that has changed with time, or to a drop in the birth rate in subpopulations showing enrichment of the mutation, or to both of these causes. 38 refs., 4 figs., 2 tabs.

  15. [A 74-year-old woman with macrocytic anemia].

    PubMed

    Picardi, A; Navajas, F; Spoto, S; Palma Modoni, A; De Galasso, L; Costantino, S

    2002-01-01

    A seventy-four years old woman is assessed for asthenia, fatigue, non ulcerous dyspepsia with macrocytic anemia. The patient's medical history taking in Binswanger disease--diagnosed 5 aa before-, epilepsy-2 aa before- and a previous episode of TVP of the left leg, suggested the hypothesis that a B12 deficiency, by a chronic gastritis, would involve an increase of homocysteine cause of the clinical manifestations of megaloblastic anemia, Binswanger disease, tardive epilepsy and previous TVP. The fisic and blood and instrumental exams confirmed the clinical diagnosis. The patient is having vitamin B12.

  16. Addison disease

    MedlinePlus

    ... amounts of some or all of its hormones ( hypopituitarism ) Autoimmune disorder that affects the nerves and the ... disease) Dermatitis herpetiformis Diabetes Graves disease Hyperthyroidism Hypoparathyroidism Hypopituitarism Immune response Myasthenia gravis Ovarian hypofunction Pernicious anemia ...

  17. Anemia for the Primary Care Physician.

    PubMed

    Powell, Darryl J; Achebe, Maureen Okam

    2016-12-01

    Anemia denotes a reduced red blood cell (RBC) mass from any cause. The causes of anemia are numerous and due to decreased (or abnormal) erythropoesis, shortened RBC life span, or blood loss. The most common etiology of anemia is iron deficiency. A judicious work up of anemia includes evaluating the reticulocyte count and peripheral smear. The severity of illness of a patient with anemia is determined by the degree of anemia and the seriousness of the underlying disorder. Management of patients with hereditary and hemolytic anemias should involve a hematologist.

  18. Anemia and iron deficiency in heart failure.

    PubMed

    Gunawardena, Shanti; Dunlap, Mark E

    2012-12-01

    Anemia is a common comorbidity in heart failure (HF), and is associated with increased morbidity and mortality. However, it remains unclear whether anemia is merely a marker of poor prognosis or whether anemia itself confers risk. The pathogenesis of anemia in HF is multifactorial. Iron deficiency also confers risk in HF, either with or without associated anemia, and treatment of iron deficiency improves the functional status of patients with HF. An ongoing large clinical trial studying the use of darbepoetin-alfa in patients with anemia and systolic HF is expected to provide information that should improve our understanding of anemia in HF.

  19. Two-locus linkage analysis in multiple sclerosis (MS)

    SciTech Connect

    Tienari, P.J. Univ. of Helsinki ); Terwilliger, J.D.; Ott, J. ); Palo, J. ); Peltonen, L. )

    1994-01-15

    One of the major challenges in genetic linkage analyses is the study of complex diseases. The authors demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, they have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family member than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested. 41 refs., 6 tabs.

  20. Pure red cell aplasia following autoimmune hemolytic anemia: an enigma.

    PubMed

    Saha, M; Ray, S; Kundu, S; Chakrabarti, P

    2013-01-01

    A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA), prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA) showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

  1. Oral and Dental Considerations in Management of Sickle Cell Anemia

    PubMed Central

    2015-01-01

    ABSTRACT Sickle cell anemia is a genetic disease that primarily affects the black population. This anemia is due to a homozygous state of the abnormal hemoglobin S. An alteration occurs on the DNA molecule involving the substitution of the amino acid valine for glutamic acid at the sixth position on the beta polypeptide chain. This biochemical variation on the DNA molecule creates a physiological change that causes sickle-shaped red blood cells to be produced. The sickle-shaped cells are the result of the hemoglobin S being deoxygenated. This case report presents a case of 16-year-old female with sickle cell disease and its dental management. How to cite this article: Acharya S. Oral and Dental Considerations in Management of Sickle Cell Anemia. Int J Clin Pediatr Dent 2015;8(2):141-144. PMID:26379384

  2. Severe autoimmune hemolytic anemia with renal neoplasm.

    PubMed

    Rhodes, Emily C; Parikh, Sahil P; Bhattacharyya, Nishith

    2014-02-01

    Autoimmune hemolytic anemia is a type of hemolytic anemia characterized by autoantibodies directed against red blood cells shortening their survival. When autoimmune hemolytic anemia is secondary to a paraneoplastic process, severe anemia can occur leading to significant morbidity and even mortality. Here we discuss the literature and present the case of a child with autoimmune hemolytic anemia from a paraneoplastic syndrome secondary to a renal tumor.

  3. Sickle Cell Disease

    MedlinePlus

    ... in families). It causes a type of abnormal hemoglobin (a protein found in red blood cells). Hemoglobin carries oxygen in the blood. Normal red blood ... betathalassemia, chronic hemolytic anemia, drepanocytic anemia, Hb S disease, ... disease, hemoglobin SC disease, hemoglobin SS disease, hemoglobin synthesis, ...

  4. Prevalence and incidence of anemia in the German Heinz Nixdorf Recall Study.

    PubMed

    Eisele, Lewin; Dürig, Jan; Broecker-Preuss, Martina; Dührsen, Ulrich; Bokhof, Beate; Erbel, Raimund; Moebus, Susanne; Jöckel, Karl-Heinz

    2013-06-01

    This study aims to determine prevalence and incidence of anemia in the general population in Germany and evaluate a potential role of serum-free light chains (FLC) as biomarker in anemia. The population-based Heinz Nixdorf Recall Study comprises 4,814 men and women aged 45-75 years. Hemoglobin <13 g/dl in men and <12 g/dl in women defined anemia. Laboratory data was used to classify cases into renal, iron deficiency (IDA), vitamin B12/folic acid deficiency, anemia of chronic disease (ACD), and unexplained anemia (UA). Follow-up data was available from annual questionnaires, death certificates, and 5-year follow-up visit (5-year FU). Anemia cases (152) were identified (prevalence 3.2 %, 95 % CI 2.7-3.7). In participants aged 65 or older, prevalence was 4.3 % (95 % CI 2.9-6.0) in both men and women. Main anemia subtypes were: IDA 19 %, ACD 25 %, and UA 44 %. Incidence increased with age and was 12.8/1,000 person-years and 10.9/1,000 person-years in men and women aged 65 or older, respectively. UA was characterized by elevated FLC. Participants with elevated FLC and high-sensitivity C-reactive protein (hsCRP) had an increased risk of anemia at 5-year FU. FLC-alone or in combination with hsCRP-may serve as biomarker indicating an increased risk of developing anemia.

  5. A suppressor locus for MODY3-diabetes

    PubMed Central

    Garcia-Gonzalez, Miguel A.; Carette, Claire; Bagattin, Alessia; Chiral, Magali; Makinistoglu, Munevver Parla; Garbay, Serge; Prévost, Géraldine; Madaras, Cécile; Hérault, Yann; Leibovici, Michel; Pontoglio, Marco

    2016-01-01

    Maturity Onset Diabetes of the Young type 3 (MODY3), linked to mutations in the transcription factor HNF1A, is the most prevalent form of monogenic diabetes mellitus. HNF1alpha-deficiency leads to defective insulin secretion via a molecular mechanism that is still not completely understood. Moreover, in MODY3 patients the severity of insulin secretion can be extremely variable even in the same kindred, indicating that modifier genes may control the onset of the disease. With the use of a mouse model for HNF1alpha-deficiency, we show here that specific genetic backgrounds (C3H and CBA) carry a powerful genetic suppressor of diabetes. A genome scan analysis led to the identification of a major suppressor locus on chromosome 3 (Moda1). Moda1 locus contains 11 genes with non-synonymous SNPs that significantly interacts with other loci on chromosomes 4, 11 and 18. Mechanistically, the absence of HNF1alpha in diabetic-prone (sensitive) strains leads to postnatal defective islets growth that is remarkably restored in resistant strains. Our findings are relevant to human genetics since Moda1 is syntenic with a human locus identified by genome wide association studies of fasting glycemia in patients. Most importantly, our results show that a single genetic locus can completely suppress diabetes in Hnf1a-deficiency. PMID:27667715

  6. Fanconi anemia: current management.

    PubMed

    Kook, Hoon

    2005-01-01

    Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder, characterized by congenital anomalies, defective hematopoiesis and a high risk of developing acute myeloid leukemia and certain solid tumors. All racial and ethnic groups are at risk, and at least 11 complementation groups have been identified and the genes defective in eight of these have been identified (FANCA, C, D2, E, F, G, L and BRCA2). FA-A is the most common complementation group, accounting for approximately 65% of all affected individuals. The gold-standard screening test for FA is based on the characteristic hypersensitivity of FA cells to the crosslinking agents, such as mitomicin C or diepoxybutane. Recent progress has been made in identifying the genes bearing pathogenetically relevant mutations, but slower progress has been made in defining the precise functions of the proteins in normal cells, in part because that the proteins are multifunctional. Molecular studies have established that a common pathway exist, both between the FA proteins and other proteins involved in DNA repair such as NBS1, ATM, BRCA1 and BRCA2. Stem cell transplantation (SCT) is the only option for establishing normal hematopoiesis. To reduce undue toxicities due to inherent hypersensitivity, nonmyeloablative conditioning for transplants has been advocated. This review summarizes the general clinical and hematologic features and the current management of FA. Fanconi anemia (FA) is the commonest type of inherited bone marrow failure syndrome with the birth incidence of around three per million. The inheritance pattern is autosomal recessive with the estimated heterozygote frequency being one in 300 in Europe and the US.

  7. Iron, anemia and hepcidin in malaria

    PubMed Central

    Spottiswoode, Natasha; Duffy, Patrick E.; Drakesmith, Hal

    2014-01-01

    Malaria and iron have a complex but important relationship. Plasmodium proliferation requires iron, both during the clinically silent liver stage of growth and in the disease-associated phase of erythrocyte infection. Precisely how the protozoan acquires its iron from its mammalian host remains unclear, but iron chelators can inhibit pathogen growth in vitro and in animal models. In humans, iron deficiency appears to protect against severe malaria, while iron supplementation increases risks of infection and disease. Malaria itself causes profound disturbances in physiological iron distribution and utilization, through mechanisms that include hemolysis, release of heme, dyserythropoiesis, anemia, deposition of iron in macrophages, and inhibition of dietary iron absorption. These effects have significant consequences. Malarial anemia is a major global health problem, especially in children, that remains incompletely understood and is not straightforward to treat. Furthermore, the changes in iron metabolism during a malaria infection may modulate susceptibility to co-infections. The release of heme and accumulation of iron in granulocytes may explain increased vulnerability to non-typhoidal Salmonella during malaria. The redistribution of iron away from hepatocytes and into macrophages may confer host resistance to superinfection, whereby blood-stage parasitemia prevents the development of a second liver-stage Plasmodium infection in the same organism. Key to understanding the pathophysiology of iron metabolism in malaria is the activity of the iron regulatory hormone hepcidin. Hepcidin is upregulated during blood-stage parasitemia and likely mediates much of the iron redistribution that accompanies disease. Understanding the regulation and role of hepcidin may offer new opportunities to combat malaria and formulate better approaches to treat anemia in the developing world. PMID:24910614

  8. Genetics Home Reference: Fanconi anemia

    MedlinePlus

    ... increased risk of developing a cancer of blood-forming cells in the bone marrow called acute myeloid ... PubMed or Free article on PubMed Central Kitao H, Takata M. Fanconi anemia: a disorder defective in ...

  9. Hyper-variation of Tandem Repeats at the PD0218 (pspB) locus of Xylella fastidiosa Almond Leaf Scorch and Grape Pierce’s Disease Strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Xylella fastidiosa is a Gram negative plant pathogenic bacterium that causes almond leaf scorch disease (ALSD) and grape Pierce’s disease (PD) in California. A-genotype strains cause ALSD only. G-genotype strains cause both PD and ALSD. Little is known about how X. fastidiosa interacts with the envi...

  10. Fine scale genetic and physical mapping using interstitial deletion mutants of Lr34 /Yr18: a disease resistance locus effective against multiple pathogens in wheat.

    PubMed

    Spielmeyer, W; Singh, R P; McFadden, H; Wellings, C R; Huerta-Espino, J; Kong, X; Appels, R; Lagudah, E S

    2008-02-01

    The Lr34/Yr18 locus has contributed to durable, non-race specific resistance against leaf rust (Puccinia triticina) and stripe rust (P. striiformis f. sp. tritici) in wheat (Triticum aestivum). Lr34/Yr18 also cosegregates with resistance to powdery mildew (Pm38) and a leaf tip necrosis phenotype (Ltn1). Using a high resolution mapping family from a cross between near-isogenic lines in the "Thatcher" background we demonstrated that Lr34/Yr18 also cosegregated with stem rust resistance in the field. Lr34/Yr18 probably interacts with unlinked genes to provide enhanced stem rust resistance in "Thatcher". In view of the relatively low levels of DNA polymorphism reported in the Lr34/Yr18 region, gamma irradiation of the single chromosome substitution line, Lalbahadur(Parula7D) that carries Lr34/Yr18 was used to generate several mutant lines. Characterisation of the mutants revealed a range of highly informative genotypes, which included variable size deletions and an overlapping set of interstitial deletions. The mutants enabled a large number of wheat EST derived markers to be mapped and define a relatively small physical region on chromosome 7DS that carried Lr34/Yr18. Fine scale genetic mapping confirmed the physical mapping and identified a genetic interval of less than 0.5 cM, which contained Lr34/Yr18. Both rice and Brachypodium genome sequences provided useful information for fine mapping of ESTs in wheat. Gene order was more conserved between wheat and Brachypodium than with rice but these smaller grass genomes did not reveal sequence information that could be used to identify a candidate gene for rust resistance in wheat. We predict that Lr34/Yr18 is located within a large insertion in wheat not found at syntenic positions in Brachypodium and rice.

  11. Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia.

    PubMed

    Shidfar, Farzad; Amani, Samira; Vafa, Mohammadreza; Shekarriz, Ramin; Hosseini, Sharieh; Shidfar, Shahrzad; Eshraghian, Mohammadreza; Mousavi, Seyedeh Neda

    2016-01-01

    Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15-45 years, were included. The patients were randomly assigned to receive 500 mg of DHA supplement or placebo with an iron tablet, once daily for 12 weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA.

  12. Castleman-Kojima disease (TAFRO syndrome) : a novel systemic inflammatory disease characterized by a constellation of symptoms, namely, thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly : a status report and summary of Fukushima (6 June, 2012) and Nagoya meetings (22 September, 2012).

    PubMed

    Kawabata, Hiroshi; Takai, Kazue; Kojima, Masaru; Nakamura, Naoya; Aoki, Sadao; Nakamura, Shigeo; Kinoshita, Tomohiro; Masaki, Yasufumi

    2013-01-01

    Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, microcytic anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. [J Clin Exp Hematop 53(1): 57-61, 2013].

  13. [Anaemia and chronic diseases].

    PubMed

    Chassagne, Philippe; Amalou, Laetitia; Thillard, Anne-Lyse; Gbaguidi, Xavier; Roca, Frédéric

    2015-03-01

    The prevalence of anemia in old patients is 20%. Anemia is mostly multifactorial associated with multiple comorbidities that are frequently observed in people of 65 years or older. Chronic renal failure, inflammatory diseases, nutrient deficiencies and especially iron deficiency are the most associated conditions with anemia. Anemia represents a prognosis marker of general health in old people. Thus anemia is associated with higher rates of morbidities (such as unplanned hospitalizations) and greatest mortality. Therefore anemia could be considered either as a consequence of chronic diseases or a prognosis marker of their severity. The prognosis of chronic cardiac failure is for example worst in anemic patients. Finally anemia is listed as a component of the frailty.

  14. What Are the Signs and Symptoms of Anemia?

    MedlinePlus

    ... Twitter. What Are the Signs and Symptoms of Anemia? The most common symptom of anemia is fatigue ( ... mild symptoms or none at all. Complications of Anemia Some people who have anemia may have arrhythmias ( ...

  15. Genetics Home Reference: iron-refractory iron deficiency anemia

    MedlinePlus

    ... refractory iron deficiency anemia iron-refractory iron deficiency anemia Enable Javascript to view the expand/collapse boxes. ... All Close All Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  16. On the road to gene therapy for beta-thalassemia and sickle cell anemia.

    PubMed

    Bank, Arthur

    2008-01-01

    Human globin gene therapy is a potential cure for sickle cell disease and beta-thalassemia (Cooley anemia). A clinical trial of this treatment is currently under way in Paris using lentiglobin vectors.

  17. Evidencing the Role of Erythrocytic Apoptosis in Malarial Anemia

    PubMed Central

    Totino, Paulo R. R.; Daniel-Ribeiro, Cláudio T.; Ferreira-da-Cruz, Maria de Fátima

    2016-01-01

    In the last decade it has become clear that, similarly to nucleated cells, enucleated red blood cells (RBCs) are susceptible to programmed apoptotic cell death. Erythrocytic apoptosis seems to play a role in physiological clearance of aged RBCs, but it may also be implicated in anemia of different etiological sources including drug therapy and infectious diseases. In malaria, severe anemia is a common complication leading to death of children and pregnant women living in malaria-endemic regions of Africa. The pathogenesis of malarial anemia is multifactorial and involves both ineffective production of RBCs by the bone marrow and premature elimination of non-parasitized RBCs, phenomena potentially associated with apoptosis. In the present overview, we discuss evidences associating erythrocytic apoptosis with the pathogenesis of severe malarial anemia, as well as with regulation of parasite clearance in malaria. Efforts to understand the role of erythrocytic apoptosis in malarial anemia can help to identify potential targets for therapeutic intervention based on apoptotic pathways and consequently, mitigate the harmful impact of malaria in global public health. PMID:28018860

  18. Trisomy 1q in a patient with severe aplastic anemia.

    PubMed

    Angelidis, Prodromos; Kojouri, Kiarash; Lee, Jiyun; Kern, William; Mulvihill, John J; Li, Shibo

    2006-08-01

    Aplastic anemia is a rare, serious disease characterized by hypocellular bone marrow and pancytopenia in the peripheral blood. Most cases are acquired, idiopathic, and without gross cytogenetic abnormalities. A few chromosome abnormalities have recurred among a small subset of patients, most commonly trisomy 8 and monosomy 7. Some of these chromosome abnormalities have prognostic and therapeutic significance, although for most the clinical relevance is not known. We present the case of a 40-year-old man with idiopathic severe aplastic anemia in bone marrow cells with trisomy of the whole long arm of chromosome 1 due to an unbalanced translocation between chromosomes 1 and 15 at breakpoints of q10 and 15q10. This clonal abnormality (which, to our knowledge, has not been previously reported in a patient with aplastic anemia) suggests that genes on 1q may be involved in marrow aplasia.

  19. [Severe chronic anemia and endocrine disorders in children].

    PubMed

    Hauschild, Michael; Theintz, Gérald

    2007-04-18

    Hemolytic anemias can induce various anomalies of the endocrine glands which can already be observed in children. Endocrine dysfunction is also found in the course of therapy for aplastic anemias, usually as undesirable side effects. In Europe, 2-9% of the population belongs to ethnic minorities at risk for developing hemolytic anemia. Pituitary affinity to iron deposition explains the high incidence of hypogonadism, puberty delay and growth retardation although other factors have to be considered. Growth hormone deficiency has to be ruled out as it can occur in a minority of subjects with thalassemia and sickle-cell disease (drepanocytosis). Diabetes mellitus, hypothyroidism and hypoparathyroidism may also develop. Follow-up includes close monitoring of growth and pubertal development in order to guide therapeutic interventions.

  20. A 4. 5-megabase yeast artificial chromosome contig from human chromosome 13q14. 3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus

    SciTech Connect

    White, A.; Tomfohrde, J.; Barnes, R. ); Stewart, E.; Cavalli-Sforza, L. ); Le Paslier, D. ); Weissenbach, J. ); Farrer, L. ); Bowcock, A. Eugene McDermott Center of Human Growth and Development, Dallas, TX )

    1993-11-15

    The authors have previously performed a genetic analysis of multiply affected families to map a locus responsible for Wilson disease (WND) to a 0.3-centimorgan (cM) region within chromosome 13q14.3, between D12S31 and D13S59. Here they describe the construction of a contig of [approx]4.5 Mb, which spans this region and extends from D13S25 to D13S59. This contig consists of 28 genomic yeast artificial chromosome (YAC) clones. Five critical crossover events have been defined in this interval in two unaffected (Centre d'Etudes du Polymorphisme Humain) and three WND families. The combination of sequence tagged site content mapping of YACs with both polymorphic and nonpolymorphic markers and recombination breakpoint mapping resulted in the following order of polymorphic markers: centromere-RB1-D13S25-AFM205vh2-D13S31-D13S227-D13S228-AFM238vc3-D13S133-AFM084xc5-D13S137-D13S169, D13S155-D13S59-telomere. The recombination/physical distance ratio varies from [approx] 3000 kb per cM in the region between D13S31 and D13S25 to 6000 kb per cM in the region between D13S31 and D13S59. Three WND families exhibiting recombination between the disease locus and D13S31 or D13S59 were genotyped for additional markers in this region and further refined the location of the WND gene to between D13S155 and D13S133. Nine of the markers in this region of <1 cM are polymorphic microsatellites (seven have observed heterozygosities of 70% or above) that will be extremely useful in prenatal and preclinical diagnosis of this disease. This physical map is an essential step in the isolation of the WND gene and is a framework for the identification of candidate genes.

  1. [Genetic aspects of sickle cell anemia].

    PubMed

    Labie, D

    1992-10-01

    The genetics of sickle cell anemia may be considered as a model. Its mendelian transmission was hypothesized even before the molecular era. Once the mutation identified, it could be studied at the protein and DNA level; a consistent pathophysiological mechanism was proposed; the various genetic forms of the disease could be identified; the way by which a balanced polymorphism with Plasmodium falciparum malaria is obtained was analyzed. More recently, investigations were run in order to understand how modulating, or epistatic factors could modify the pathophysiological mechanism and contribute to the high clinical diversity of the disease. Several factors have been identified, among which a concomitant alpha-thalassemia, an overproduction of fetal hemoglobin, due either to an activation of the gamma genes or to an increase of the F-cell number, and finally a quantitative control of the beta s chains themselves. Such a high number of genetic active factors questions the concept itself of a monogenic disease.

  2. [Cardiopulmonary complications in sickle cell anemia].

    PubMed

    Rojas-Jiménez, Sara; Lopera-Valle, Johan; Yabur-Espítia, Mirna

    2013-01-01

    Sickle cell anemia, considered the most prevalent genetic disease among African Americans, is a disease with autosomal recessive inheritance pattern, characterized by the production of hemoglobin S. This abnormal protein polymerizes and facilitates the formation of fibrillar aggregates that alters the erythrocyte morphology. The stiffness of the red blood cells hinders the adequate transit across microcirculation, leading to hemolysis and increased blood viscosity, which ease thrombogenesis and vascular occlusion, resulting in tissue ischemia and microinfarcts. This disease has a high rate of morbidity and mortality, especially in the first three years of life, when a rapid diagnosis and appropriate treatment are essential. Cardiovascular complications such as heart failure and pulmonary hypertension may develop independently, and each one contributes to increased mortality, being the combination of both risk factors, an important aggravating factor for prognosis and a determinant indicator of mortality.

  3. In situ localization of the genetic locus encoding the lysosomal acid lipase/cholesteryl esterase (LIPA) deficient in wolman disease to chromosome 10q23. 2-q23. 3

    SciTech Connect

    Anderson, R.A.; Rao, N.; Byrum, R.S.; Rothschild, C.B.; Bowden, D.W.; Hayworth, R.; Pettenati, M. )

    1993-01-01

    Human acid lipase/cholesteryl esterase (EC 3.1.1.13) is a 46-kDa glycoprotein required for the lysosomal hydrolysis of cholesteryl esters and triglycerides that cells acquire through the receptor-mediated endocytosis of low-density lipoproteins. This activity is essential in the provision of free cholesterol for cell metabolism as well as for the feedback signal that modulates endogenous cellular cholesterol production. The extremely low level of lysosomal acid lipase in patients afflicted with the hereditary, allelic lysosomal storage disorders Woman disease (WD) and cholesteryl ester storage disease (CESD) (MIM Number 278000 (6)) is associated with the massive intralysosomal lipid storage and derangements in the regulation of cellular cholesterol production (10). Both WD and CESD cells lack a specific acid lipase isoenzyme and it is thought that the different mutations associated with WD and CESD are in the structural gene for this isoenzyme, LIPA. Analysis of the activity of the acid lipase isoenzyme in cell extracts from human-Chinese hamster somatic cell hybrids (4, 11) demonstrated the concordant segregation of the gene locus for lysosomal acid lipase with the glutamate oxaloacetate transaminase-1 (GOT1) enzyme marker for human chromosome 10 which was subsequently localized to 10q24.1 q25.1 (8). 11 refs., 1 figs.

  4. Development of a disease-specific quality of life questionnaire for patients with aplastic anemia and/or paroxysmal nocturnal hemoglobinuria (QLQ-AA/PNH)-report on phases I and II.

    PubMed

    Groth, Martha; Singer, Susanne; Niedeggen, Cathrin; Petermann-Meyer, Andrea; Röth, Alexander; Schrezenmeier, Hubert; Höchsmann, Britta; Brümmendorf, Tim H; Panse, Jens

    2017-02-01

    Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are interrelated ultra-rare diseases. Quality of life (QoL) evaluation tools used in studies for AA and PNH are unspecific and designed for cancer patients (e.g., the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30). Given the complexity of AA and PNH, variation in symptoms and treatments, younger age of many patients, and the fact that AA and PNH are not classified as malignant diseases, it is likely that cancer-specific questionnaires are inappropriate. We generate an AA/PNH-specific QoL questionnaire (QLQ-AA/PNH), performed according to EORTC guidelines. QoL issues were obtained from the literature and interviews with patients and physicians (phase I), then ranked by patients and physicians. In phase II, items were created. Patients in more than 25 German and Swiss cities were interviewed face to face. In phase I, interviews of 19 patients and 8 physicians specialized in AA/PNH treatment resulted in 649 QoL issues; these were condensed to 175 and graded according to their importance by 30 patients and 14 physicians (phase II). Five physicians took part in phases I and II. Altogether, 97 issues were rated important. Twelve EORTC QLQ-C30 items were not rated important, while several new QoL aspects were brought up. Modifications in wording and phrasing led to two questionnaires with 77 items regarding general QoL aspects and 20 items regarding medical care. Important QoL aspects of PNH/AA patients are inappropriately captured with available QoL tools. Developing a new QoL questionnaire specific for this patient group is warranted.

  5. Identification of shared genetic susceptibility locus for coronary artery disease, type 2 diabetes and obesity: a meta-analysis of genome-wide studies.

    PubMed

    Wu, Chaoneng; Gong, Yunguo; Yuan, Jie; Gong, Hui; Zou, Yunzeng; Ge, Junbo

    2012-06-14

    Type 2 diabetes (2DM), obesity, and coronary artery disease (CAD) are frequently coexisted being as key components of metabolic syndrome. Whether there is shared genetic background underlying these diseases remained unclear. We performed a meta-analysis of 35 genome screens for 2DM, 36 for obesity or body mass index (BMI)-defined obesity, and 21 for CAD using genome search meta-analysis (GSMA), which combines linkage results to identify regions with only weak evidence and provide genetic interactions among different diseases. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to the best linkage evidence within each bin. For each disease, bin 6.2 achieved genomic significanct evidence, and bin 9.3, 10.5, 16.3 reached suggestive level for 2DM. Bin 11.2 and 16.3, and bin 10.5 and 9.3, reached suggestive evidence for obesity and CAD respectively. In pooled all three diseases, bin 9.3 and 6.5 reached genomic significant and suggestive evidence respectively, being relatively much weaker for 2DM/CAD or 2DM/obesity or CAD/obesity. Further, genomewide significant evidence was observed of bin 16.3 and 4.5 for 2DM/obesity, which is decreased when CAD was added. These findings indicated that bin 9.3 and 6.5 are most likely to be shared by 2DM, obesity and CAD. And bin 16.3 and 4.5 are potentially common regions to 2DM and obesity only. The observed shared susceptibility regions imply a partly overlapping genetic aspects of disease development. Fine scanning of these regions will definitely identify more susceptibility genes and causal variants.

  6. Anemia, Heart Failure and Evidence-Based Clinical management

    PubMed Central

    Pereira, Camila Alves; Roscani, Meliza Goi; Zanati, Silméia Garcia; Matsubara, Beatriz Bojikian

    2013-01-01

    Anemia is a prevalent comorbidity and marker of a poorer prognosis in patients with heart failure (HF). Its clinical relevance, as well as its pathophysiology and the clinical management of these patients are important subjects in the specialized literature. In the present review, we describe the current concepts on the pathophysiology of anemia in HF, its diagnostic criteria, and the recommendations for iron supplementation. Also, we make a critical analysis of the major studies showing evidences on the benefits of this supplementation. The four main components of anemia are addressed: chronic disease, dilutional, "renal" and malabsorption. In patients with HF, the diagnostic criteria are the same as those used in the general population: serum ferritin levels lower than 30 mcg/L in patients without kidney diseases and lower than 100 mcg/L or serum ferritin levels between 100-299 mcg/L with transferring saturation lower than 20% in patients with chronic kidney diseases. Finally, the therapeutic possibilities for anemia in this specific patient population are discussed. PMID:23917508

  7. Allele-specific expression at the RET locus in blood and gut tissue of individuals carrying risk alleles for Hirschsprung disease.

    PubMed

    Matera, Ivana; Musso, Marco; Griseri, Paola; Rusmini, Marta; Di Duca, Marco; So, Man-Ting; Mavilio, Domenico; Miao, Xiaoping; Tam, Paul Hk; Ravazzolo, Roberto; Ceccherini, Isabella; Garcia-Barcelo, Merce

    2013-05-01

    RET common variants are associated with Hirschsprung disease (HSCR; colon aganglionosis), a congenital defect of the enteric nervous system. We analyzed a well-known HSCR-associated RET haplotype that encompasses linked alleles in coding and noncoding/regulatory sequences. This risk haplotype correlates with reduced level of RET expression when compared with the wild-type counterpart. As allele-specific expression (ASE) contributes to phenotypic variability in health and disease, we investigated whether RET ASE could contribute to the overall reduction of RET mRNA detected in carriers. We tested heterozygous neuroblastoma cell lines, ganglionic gut tissues (18 HSCR and 14 non-HSCR individuals) and peripheral blood mononuclear cells (PBMCs; 16 HSCR and 14 non-HSCR individuals). Analysis of the data generated by SNaPshot and Pyrosequencing revealed that the RET risk haplotype is significantly more expressed in gut than in PBMCs (P = 0.0045). No ASE difference was detected between patients and controls, irrespective of the sample type. Comparison of total RET expression levels between gut samples with and without ASE, correlated reduced RET expression with preferential transcription from the RET risk haplotype. Nonrandom RET ASE occurs in ganglionic gut regardless of the disease status. RET ASE should not be excluded as a disease mechanism acting during development.

  8. BMT Abatacept for Non-Malignant Diseases

    ClinicalTrials.gov

    2016-08-16

    Hurler Syndrome; Fanconi Anemia; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Shwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia; Thalassemia Major; Hemophagocytic Lymphohistiocytosis; Sickle Cell Disease

  9. Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis.

    PubMed

    Iolascon, Achille; De Falco, Luigia; Beaumont, Carole

    2009-03-01

    Microcytic anemia is the most commonly encountered anemia in general medical practice. Nutritional iron deficiency and beta thalassemia trait are the primary causes in pediatrics, whereas bleeding disorders and anemia of chronic disease are common in adulthood. Microcytic hypochromic anemia can result from a defect in globin genes, in heme synthesis, in iron availability or in iron acquisition by the erythroid precursors. These microcytic anemia can be sideroblastic or not, a trait which reflects the implications of different gene abnormalities. Iron is a trace element that may act as a redox component and therefore is integral to vital biological processes that require the transfer of electrons as in oxygen transport, oxidative phosphorylation, DNA biosynthesis and xenobiotic metabolism. However, it can also be pro-oxidant and to avoid its toxicity, iron metabolism is strictly controlled and failure of these control systems could induce iron overload or iron deficient anemia. During the past few years, several new discoveries mostly arising from human patients or mouse models have highlighted the implication of iron metabolism components in hereditary microcytic anemia, from intestinal absorption to its final inclusion into heme. In this paper we will review the new information available on the iron acquisition pathway by developing erythrocytes and its regulation, and we will consider only inherited microcytosis due to heme synthesis or to iron metabolism defects. This information could be useful in the diagnosis and classification of these microcytic anemias.

  10. Diagnosis and treatment of unexplained anemia with iron deficiency without overt bleeding.

    PubMed

    Dahlerup, Jens Frederik; Eivindson, Martin; Jacobsen, Bent Ascanius; Jensen, Nanna Martin; Jørgensen, Søren Peter; Laursen, Stig Borbjerg; Rasmussen, Morten; Nathan, Torben

    2015-04-01

    A general overview is given of the causes of anemia with iron deficiency as well as the pathogenesis of anemia and the para-clinical diagnosis of anemia. Anemia with iron deficiency but without overt GI bleeding is associated with a risk of malignant disease of the gastrointestinal tract; upper gastrointestinal cancer is 1/7 as common as colon cancer. Benign gastrointestinal causes of anemia are iron malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations. The following diagnostic strategy is recommended for unexplained anemia with iron deficiency: conduct serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing and perform bidirectional endoscopy (gastroscopy and colonoscopy). Bidirectional endoscopy is not required in premenopausal women < 40 years of age. Small intestine investigation (capsule endoscopy, CT, or MRI enterography) is not recommended routinely after negative bidirectional endoscopy but should be conducted if there are red flags indicating malignant or inflammatory small bowel disease (e.g., involuntary weight loss, abdominal pain or increased CRP). Targeted treatment of any cause of anemia with iron deficiency found on diagnostic assessment should be initiated. In addition, iron supplementation should be administered, with the goal of normalizing hemoglobin levels and replenishing iron stores. Oral treatment with a 100-200 mg daily dose of elemental iron is recommended (lower dose if side effects), but 3-6 months of oral iron therapy is often required to achieve therapeutic goals. Intravenous iron therapy is used if oral treatment lacks efficacy or causes side effects or in the presence of intestinal malabsorption or prolonged inflammation. Three algorithms are given for the following conditions: a) the paraclinical diagnosis of anemia with iron deficiency; b) the diagnostic work-up for unexplained anemia with

  11. Special Issues for People with Aplastic Anemia

    MedlinePlus

    ... aplastic anemia and are pregnant or want to get pregnant, find an aplastic anemia specialist and an obstetrician (OB) who specializes in high-risk births. Every person and every pregnancy is different. Make sure you ...

  12. Anemia caused by low iron - children

    MedlinePlus

    ... deficiency in children can also be related to lead poisoning . Symptoms Mild anemia may have no symptoms. As ... Elsevier; 2016:chap 455. Read More Anemia Hemoglobin Lead poisoning Review Date 2/11/2016 Updated by: Todd ...

  13. Drug-induced immune hemolytic anemia

    MedlinePlus

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... In some cases, a drug can cause the immune system to mistake your own red blood cells for foreign substances. The body responds by making ...

  14. Genetics Home Reference: congenital dyserythropoietic anemia

    MedlinePlus

    ... Understand Genetics Home Health Conditions CDA congenital dyserythropoietic anemia Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Congenital dyserythropoietic anemia ( CDA ) is an inherited blood disorder that affects ...

  15. FastStats: Anemia or Iron Deficiency

    MedlinePlus

    ... this? Submit What's this? Submit Button NCHS Home Anemia or Iron Deficiency Recommend on Facebook Tweet Share ... visits Number of visits to emergency departments with anemia as the primary hospital discharge diagnosis: 146,000 ...

  16. Correlation between hepcidin level and renal anemia.

    PubMed

    Yang, L-N; Zhang, P; Tang, F; Wang, G; Li, F-E

    2014-09-12

    Anemia in patients with chronic renal insufficiency (CRI) is related to the chronic inflammatory state, low iron absorption rate, and low utilization rate. As a key protein for iron metabolism, hepcidin plays an important role in CRI anemia. The study aimed to determine the correlation between hepcidin level and renal anemia. Ninety CRI anemia patients treated in our hospital from February 2012 to December 2012 were enrolled in the study to compare with a healthy control group of 40 cases by measuring the hepcidin level and analyzing the correlation between hepcidin level and CRI anemia. The hepcidin level was significantly higher in the CRI anemia group than the control group; there was a positive correlation between hepcidin level and serum ferritin as well as IL-6 level. Hepcidin level was significantly related to degree of anemia, indicating that an increase in hepcidin level will result in anemia.

  17. Magnetic resonance imaging in pediatric sickle cell anemia

    PubMed Central

    Zhang, Xinxian; Li, Chenglong; Li, Qiancheng

    2016-01-01

    Sickle cell disease is the result of altered genetic make up due to hereditary encounter and its form as homozygous sickle cell anemia is the most common and severe. The disease is characterized by chronic anemia, recurrent pain crises and vascular occlusion. Neurologically, there is a high incidence of stroke in childhood, as well as cognitive dysfunction. Newborn screening programmes and preventative treatments have allowed a much longer lifespan. However, recently, neurological research has shifted to characterizing more subtle aspects of brain development and functioning that may be critically important to the individual's quality of life. The present review article examines the neurological and neurocognitive complications of sickle cell disease, and discusses the importance of magnetic resonance imaging scans in the management of the disease. PMID:27446243

  18. (Inborn anemias of mice): Terminal progress report

    SciTech Connect

    Bernstein, S.E.

    1987-01-01

    Mutations located at 11 different chromosomal locations in the mouse all affecting hemopoiesis have been studied. These include: Hertwig's anemia (an), W-anemias (W, W/sup v/, W/sup 17J/ to W/sup 41J/), Steel anemias (Sl, Sl/sup d/, etc.), Normoblastic anemia (nb), Jaundiced (ja), Spherocytic anemias (sph, sph/sup ha/), sph/sup 2J/, sph/sup 2BC/, Flexed-tail anemia (f), Microcytic anemia (mk), Sex-linked anemia (Sla), Alpha thallasemia (Hba/sup th/), and a hypochromic anemia associated with low transferrin levels (hpx). Our findings indicate that the erythroid defect in W-anemias stem from an intrinsic defect in the erythroid progenitor cells, and that all other erythroid hemostatic mechanisms are fully functional. Hertwig's anemia (an) is affected in a similar fashion. However, in the case of Steel anemias, the erythroid progenitors are repressed, but when transplanted to appropriate recipients were found to be fully functional. 70 refs., 4 tabs.

  19. Solenostemon monostachyus, Ipomoea involucrata and Carica papaya seed oil versus Glutathione, or Vernonia amygdalina: Methanolic extracts of novel plants for the management of sickle cell anemia disease

    PubMed Central

    2012-01-01

    Background Sickle cell disease (SCD) is a genetic disease caused by an individual inheriting an allele for sickle cell hemoglobin from both parents and is associated with unusually large numbers of immature blood cells, containing many long, thin, crescent-shaped erythrocytes. It is a disease prevalent throughout many populations. The use of medicinal plants and nutrition in managing SCD is gaining increasing attention. Methods The antisickling effects of Solenostemon monostachyus (SolMon), Carica papaya seed oil (Cari-oil) and Ipomoea involucrata (Ipocrata) in male (HbSSM) and female (HbSSF) human sickle cell blood was examined in vitro and compared with controls, or cells treated with glutathione or an antisickling plant (Vernonia amygdalina; VerMyg). Results Levels of sickle blood cells were significantly reduced (P < 0.05) in all the plant-extract treated SCD patients’ blood compared with that of untreated SCD patients. RBCs in SolMon, Ipocrata, and Cari-oil treated samples were significantly higher (P < 0.05) compared with VerMyg-treated samples. The Fe2+/Fe3+ ratio was significantly reduced (P < 0.05) in all plant extract-treated HbSSM samples compared with controls. Hemoglobin concentration was significantly increased (P < 0.05) by SolMon treatment in HbSSF compared with VerMyg. Sickle cell polymerization inhibition exhibited by SolMon was significantly higher (P < 0.05) compared with that of VerMyg in HbSSF blood. Sickle cell polymerization inhibition in SolMon and Ipocrata were significantly higher (P < 0.05) compared with VerMyg in HbSSM blood. All plant extracts significantly reduced (P < 0.05) lactate dehydrogenase activity in both HbSSM and HbSSF-treated blood. Catalase activity was significantly increased (P < 0.05) in HbSSF blood treated with Ipocrata compared with glutathione. Cari-oil treated HbSSM and HbSSF blood had significantly increased (P < 0.05) peroxidase activity compared with controls. Conclusions Methanolic extracts from S

  20. Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case–control study

    PubMed Central

    Steele, Natasha Z. R.; Geier, Ethan G.; Damotte, Vincent; Boehme, Kevin L.; Mukherjee, Shubhabrata; Crane, Paul K.; Kauwe, John S. K.; Kramer, Joel H.; Miller, Bruce L.; Hollenbach, Jill A.; Huang, Yadong

    2017-01-01

    Background Alzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations. Methods and findings Building on prior work linking the HLA to AD, we used a robust imputation method on two separate case–control cohorts to examine the relationship between HLA haplotypes and AD risk in 309 individuals (191 AD, 118 cognitively normal [CN] controls) from the San Francisco-based University of California, San Francisco (UCSF) Memory and Aging Center (collected between 1999–2015) and 11,381 individuals (5,728 AD, 5,653 CN controls) from the Alzheimer’s Disease Genetics Consortium (ADGC), a National Institute on Aging (NIA)-funded national data repository (reflecting samples collected between 1984–2012). We also examined cerebrospinal fluid (CSF) biomarker measures for patients seen between 2005–2007 and longitudinal cognitive data from the Alzheimer’s Disease Neuroimaging Initiative (n = 346, mean follow-up 3.15 ± 2.04 y in AD individuals) to assess the clinical relevance of identified risk haplotypes. The strongest association with AD risk occurred with major histocompatibility complex (MHC) haplotype A*03:01~B*07:02~DRB1*15:01~DQA1*01:02~DQB1*06:02 (p = 9.6 x 10−4, odds ratio [OR] [95% confidence interval] = 1.21 [1.08–1.37]) in the combined UCSF + ADGC cohort. Secondary analysis suggested that this effect may be driven primarily by individuals who are negative for the established AD genetic risk

  1. Identification of KCNN2 as a susceptibility locus for coronary artery aneurysms in Kawasaki disease using genome-wide association analysis.

    PubMed

    Kim, Jae-Jung; Park, Young-Mi; Yoon, Dankyu; Lee, Kyung-Yil; Seob Song, Min; Doo Lee, Hyoung; Kim, Kwi-Joo; Park, In-Sook; Nam, Hyo-Kyoung; Weon Yun, Sin; Ki Han, Myung; Mi Hong, Young; Young Jang, Gi; Lee, Jong-Keuk

    2013-08-01

    Kawasaki disease (KD) is often complicated by coronary artery lesions (CALs), including aneurysms. Because of the complications associated with KD, this disorder is the leading cause of acquired heart disease in children from developed countries. To identify genetic loci that confer a higher risk of developing CALs, we performed a case-control association study using previous genome-wide association study data for samples from KD cases only (n=186) by grouping KD patients without CALs (control: n=123) vs KD patients with extremely large aneurysms (diameter>5 mm) (case: n=17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P<1 × 10(-5)). Of these, an SNP (rs17136627) in the potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 (KCNN2) at 5q22.3 was validated in 32 KD patients with large aneurysms (diameter>5 mm) and 191 KD patients without CALs (odds ratio (OR)=12.6, P(combined)=1.96 × 10(-8)). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD.

  2. Perinatal outcome in sickle cell anemia: a prospective study from India.

    PubMed

    Daigavane, Mayoor M; Jena, Rabindra K; Kar, Tushar J

    2013-01-01

    Sickle cell anemia, the homozygous genotype of sickle cell disease is one of the most common heritable diseases in the world. The Arab-Asian haplotype present in India is one of the least severe of all haplotypes. Many sickle cell anemia patients are now leading a symptom-free productive life due to hydroxyurea (HU) and better supportive care. Although pregnancy in sickle cell anemia patients is considered a high-risk category, it perinatal outcome is least studied, particularly among carriers of the Arab-Asian haplotype. Thus, the present prospective, randomized study was performed to assess the perinatal outcome in sickle cell anemia. Neonatal outcome such as low birth weight, perinatal mortality rate, special care newborn unit (SCNU) admission, intrauterine growth retardation (IUGR) and pre term births were significantly higher in sickle cell anemia mothers. Maternal outcome such as severe anemia, preeclampsia, vasoocclusive crisis (VOC), pulmonary complications, jaundice and blood transfusion requirements were significantly higher in sickle cell anemia mothers, which were successfully managed. Cesarian section rate was not significantly different from normal controls. Successful pregnancies were achieved in 84.44% of cases. However, we strongly recommend that pregnancies in these patients should be managed in an institutional setup.

  3. Low serum selenium is associated with anemia among older adults in the United States

    PubMed Central

    Semba, RD; Ricks, MO; Ferrucci, L; Xue, Q-L; Guralnik, JM; Fried, LP

    2009-01-01

    Objective We hypothesized that low serum selenium was associated with anemia in humans. Subjects A total of 2092 adults aged 65 and older, in the third National Nutrition Examination Survey, Phase 2 (1991–1994) (NHANES III). Methods Examination of the relationship between serum selenium and hematological indices in NHANES III. Results Anemia, defined by World Health Organization criteria, was present in 12.9%. Mean serum selenium among non-anemic and anemic adults was 1.60 and 1.51 μmol l−1 (P=0.0003). The prevalence of anemia among adults in the lowest to highest quartiles of serum selenium was 18.3, 9.5, 9.7 and 6.9%, respectively (P=0.0005). The proportion of adults in the lowest quartile of selenium among those who were non-anemic or who had anemia due to nutritional causes, chronic inflammation, renal disease or unexplained anemia was 9.9, 27.5, 17.5, 24.0 and 15.4%, respectively. An increase in loge selenium was associated with a reduced risk of anemia (odds ratio per one standard deviation increase 0.75, 95% confidence interval 0.58–0.97, P=0.03), adjusting for age, race, education, body mass index and chronic diseases. Conclusion Low serum selenium is independently associated with anemia among older men and women in the United States. PMID:17805227

  4. The central role of macrophages in trypanosomiasis-associated anemia: rationale for therapeutical approaches.

    PubMed

    Stijlemans, Benoît; Vankrunkelsven, Ann; Caljon, Guy; Bockstal, Viki; Guilliams, Martin; Bosschaerts, Tom; Beschin, Alain; Raes, Geert; Magez, Stefan; De Baetselier, Patrick

    2010-03-01

    Bovine African trypanosomiasis causes severe economical problems on the African continent and one of the most prominent immunopathological parameters associated with this parasitic infection is anemia. In this report we review the current knowledge of the mechanisms underlying trypanosomiasis-associated anemia. In first instance, the central role of macrophages and particularly their activation state in determining the outcome of the disease (i.e. trypanosusceptibility versus trypanotolerance) will be discussed. In essence, while persistence of classically activated macrophages (M1) contributes to anemia development, switching towards alternatively activated macrophages (M2) alleviates pathology including anemia. Secondly, while parasite-derived glycolipids such as the glycosylphosphatidylinositol (GPI) induce M1, host-derived IL-10 blocks M1-mediated inflammation, promotes M2 development and prevents anemia development. In this context, strategies aimed at inducing the M1 to M2 switch, such as GPI-based treatment, adenoviral delivery of IL-10 and induction of IL-10 producing regulatory T cells will be discussed. Finally, the crucial role of iron-homeostasis in trypanosomiasis-associated anemia development will be documented to stress the analogy with anemia of chronic disease (ACD), hereby providing new insight that might contribute to the treatment of ACD.

  5. Diagnosis and treatment of sideroblastic anemias: from defective heme synthesis to abnormal RNA splicing.

    PubMed

    Cazzola, Mario; Malcovati, Luca

    2015-01-01

    The sideroblastic anemias are a heterogeneous group of inherited and acquired disorders characterized by the presence of ring sideroblasts in the bone marrow. X-linked sideroblastic anemia (XLSA) is caused by germline mutations in ALAS2. Hemizygous males have a hypochromic microcytic anemia, which is generally mild to moderate and is caused by defective heme synthesis and ineffective erythropoiesis. XLSA is a typical iron-loading anemia; although most patients are responsive to pyridoxine, treatment of iron overload is also important in the management of these patients. Autosomal recessive sideroblastic anemia attributable to mutations in SLC25A38, a member of the mitochondrial carrier family, is a severe disease: patients present in infancy with microcytic anemia, which soon becomes transfusion dependent. Conservative therapy includes regular red cell transfusion and iron chelation, whereas allogenic stem cell transplantation represents the only curative treatment. Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome characterized mainly by anemia attributable to ineffective erythropoiesis. The clinical course of RARS is generally indolent, but there is a tendency to worsening of anemia over time, so that most patients become transfusion dependent in the long run. More than 90% of these patients carry somatic mutations in SF3B1, a gene encoding a core component of the RNA splicing machinery. These mutations cause misrecognition of 3' splice sites in downstream genes, resulting in truncated gene products and/or decreased expression attributable to nonsense-mediated RNA decay; this explains the multifactorial pathogenesis of RARS. Variants of RARS include refractory cytopenia with multilineage dysplasia and ring sideroblasts, and RARS associated with marked thrombocytosis; these variants involve additional genetic lesions. Inhibitors of molecules of the transforming growth factor-β superfamily have been shown recently to target ineffective

  6. Association of mild anemia with hospitalization and mortality in the elderly: the Health and Anemia population-based study

    PubMed Central

    Riva, Emma; Tettamanti, Mauro; Mosconi, Paola; Apolone, Giovanni; Gandini, Francesca; Nobili, Alessandro; Tallone, Maria Vittoria; Detoma, Paolo; Giacomin, Adriano; Clerico, Mario; Tempia, Patrizia; Guala, Adriano; Fasolo, Gilberto; Lucca, Ugo

    2009-01-01

    Background Mild anemia is a frequent laboratory finding in the elderly usually disregarded in everyday practice as an innocent bystander. The aim of the present population-based study was to prospectively investigate the association of mild grade anemia with hospitalization and mortality. Design and Methods A prospective population-based study of all 65 to 84 year old residents in Biella, Italy was performed between 2003 and 2007. Data from a total of 7,536 elderly with blood tests were available to estimate mortality; full health information available to evaluate health-related outcomes was available for 4,501 of these elderly subjects. Mild grade anemia was defined as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men. Results The risk of hospitalization in the 3 years following recruitment was higher among the mildly anemic elderly subjects than among subjects who were not anemic (adjusted hazard ratio: 1.32; 95% confidence interval: 1.09–1.60). Mortality risk in the following 3.5 years was also higher among the mildly anemic elderly (adjusted hazard ratio: 1.86; 95% confidence interval: 1.34–2.53). Similar results were found when slightly elevating the lower limit of normal hemoglobin concentration to 12.2 g/dL in women and to 13.2 g/dL in men. The risk of mortality was significantly increased in mild anemia of chronic disease but not in that due to β-thalassemia minor. Conclusions After controlling for many potential confounders, mild grade anemia was found to be prospectively associated with clinically relevant outcomes such as increased risk of hospitalization and all-cause mortality. Whether raising hemoglobin concentrations can reduce the risks associated with mild anemia should be tested in controlled clinical trials. PMID:19001283

  7. Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16

    PubMed Central

    Cordell, Heather J.; Bentham, Jamie; Topf, Ana; Zelenika, Diana; Heath, Simon; Mamasoula, Chrysovalanto; Cosgrove, Catherine; Blue, Gillian; Granados-Riveron, Javier; Setchfield, Kerry; Thornborough, Chris; Breckpot, Jeroen; Soemedi, Rachel; Martin, Ruairidh; Rahman, Thahira J.; Hall, Darroch; van Engelen, Klaartje; Moorman, Antoon F.M.; Zwinderman, Aelko H; Barnett, Phil; Koopmann, Tamara T.; Adriaens, Michiel E.; Varro, Andras; George, Alfred L.; dos Remedios, Christobal; Bishopric, Nanette H.; Bezzina, Connie R.; O’Sullivan, John; Gewillig, Marc; Bu’Lock, Frances A.; Winlaw, David; Bhattacharya, Shoumo; Devriendt, Koen; Brook, J. David; Mulder, Barbara J.M.; Mital, Seema; Postma, Alex V.; Lathrop, G. Mark; Farrall, Martin; Goodship, Judith A.; Keavney, Bernard D.

    2013-01-01

    We carried out a genome-wide association study (GWAS) of congenital heart disease (CHD). Our discovery cohort comprised 1,995 CHD cases and 5,159 controls, and included patients from each of the three major clinical CHD categories (septal, obstructive and cyanotic defects). When all CHD phenotypes were considered together, no regions achieved genome-wide significant association. However, a region on chromosome 4p16, adjacent to the MSX1 and STX18 genes, was associated (P=9.5×10−7) with the risk of ostium secundum atrial septal defect (ASD) in the discovery cohort (N=340 cases), and this was replicated in a further 417 ASD cases and 2520 controls (replication P=5.0×10−5; OR in replication cohort 1.40 [95% CI 1.19-1.65]; combined P=2.6×10−10). Genotype accounted for ~9% of the population attributable risk of ASD. PMID:23708191

  8. The 4p16.3 Parkinson Disease Risk Locus Is Associated with GAK Expression and Genes Involved with the Synaptic Vesicle Membrane

    PubMed Central

    Nagle, Michael W.; Latourelle, Jeanne C.; Labadorf, Adam; Dumitriu, Alexandra; Hadzi, Tiffany C.; Beach, Thomas G.; Myers, Richard H.

    2016-01-01

    Genome-wide association studies (GWAS) have identified the GAK/DGKQ/IDUA region on 4p16.3 among the top three risk loci for Parkinson’s disease (PD), but the specific gene and risk mechanism are unclear. Here, we report transcripts containing the 3’ clathrin-binding domain of GAK identified by RNA deep-sequencing in post-mortem human brain tissue as having increased expression in PD. Furthermore, carriers of 4p16.3 PD GWAS risk SNPs show decreased expression of one of these transcripts, GAK25 (Gencode Transcript 009), which correlates with the expression of genes functioning in the synaptic vesicle membrane. Together, these findings provide strong evidence for GAK clathrin-binding- and J-domain transcripts’ influence on PD pathogenicity, and for a role for GAK in regulating synaptic function in PD. PMID:27508417

  9. The 4p16.3 Parkinson Disease Risk Locus Is Associated with GAK Expression and Genes Involved with the Synaptic Vesicle Membrane.

    PubMed

    Nagle, Michael W; Latourelle, Jeanne C; Labadorf, Adam; Dumitriu, Alexandra; Hadzi, Tiffany C; Beach, Thomas G; Myers, Richard H

    2016-01-01

    Genome-wide association studies (GWAS) have identified the GAK/DGKQ/IDUA region on 4p16.3 among the top three risk loci for Parkinson's disease (PD), but the specific gene and risk mechanism are unclear. Here, we report transcripts containing the 3' clathrin-binding domain of GAK identified by RNA deep-sequencing in post-mortem human brain tissue as having increased expression in PD. Furthermore, carriers of 4p16.3 PD GWAS risk SNPs show decreased expression of one of these transcripts, GAK25 (Gencode Transcript 009), which correlates with the expression of genes functioning in the synaptic vesicle membrane. Together, these findings provide strong evidence for GAK clathrin-binding- and J-domain transcripts' influence on PD pathogenicity, and for a role for GAK in regulating synaptic function in PD.

  10. Diamond-Blackfan anemia, ribosome and erythropoiesis

    PubMed Central

    Costa, L. Da; Moniz, H.; Simansour, M.; Tchernia, G.; Mohandas, N.; Leblanc, T.

    2010-01-01

    Diamond-Blackfan anemia is a rare inherited bone marrow failure syndrome (5 to 7 cases/million live births) characterized by an are generative, usually macrocytic anemia with an absence or less than 5% of erythroid precursors (erythroblastopenia) in an otherwise normal bone marrow. The platelet and the white cell counts are usually normal but neutropenia, thrombopenia or thrombocytosis have been noted at diagnosis. In 40 to 50% of DBA patients, congenital abnormalities mostly in the cephalic area and in thumbs and upper limbs have been described. Recent analysis did show a phenotype/genotype correlation. Congenital erythroblastopenia of DBA is the first human disease identified to result from defects in ribosomal biogenesis. The first ribosomal gene involved in DBA, ribosomal protein (RP) gene S19 (RPS19 gene), was identified in 1999. Subsequently, mutations in 12 other RP genes out of a total of 78 RP genes have been identified in DBA. All RP gene mutations described to date are heterozygous and dominant inheritance has been documented in 40 to 45% of affected individuals. As RP mutations are yet to be identified in approximately 50% of DBA cases, it is likely that other yet to be identified genes involved in ribosomal biogenesis or other pathways may be responsible for DBA phenotype. PMID:20655265

  11. Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction

    PubMed Central

    Pu, Xiangyuan; Ren, Meixia; An, Weiwei; Zhang, Ruoxin; Yan, Shunying; Situ, Haiteng; He, Xinjie; Chen, Yequn; Tan, Xuerui; Xiao, Qingzhong; Tucker, Arthur T.; Caulfield, Mark J.; Ye, Shu

    2016-01-01

    Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD

  12. Erythema nodosum and pernicious anemia.

    PubMed

    Milman, Perry J; Goldenberg, Steven P; Scheinfeld, Noah; Pereira, Frederick A

    2013-07-14

    Erythema nodosum (EN) often presents as a sudden onset of tender, erythematous, subcutaneous nodules on the legs and ankles. Although rare, pernicious anemia may be related to vitamin B12 deficiency. Discussion of this association in the context of a particular patient is presented.

  13. [Anemia as a surgical risk factor].

    PubMed

    Moral García, Victoria; Ángeles Gil de Bernabé Sala, M; Nadia Diana, Kinast; Pericas, Bartolomé Cantallops; Nebot, Alexia Galindo

    2013-07-01

    Perioperative anemia is common in patients undergoing surgery and is associated with increased morbidity and mortality and a decreased quality of life. The main causes of anemia in the perioperative context are iron deficiency and chronic inflammation. Anemia can be aggravated by blood loss during surgery, and is most commonly treated with allogeneic transfusion. Moreover, blood transfusions are not without risks, once again increasing patient morbidity and mortality. Given these concerns, we propose to review the pathophysiology of anemia in the surgical environment, as well as its treatment through the consumption of iron-rich foods and by oral or intravenous iron therapy (iron sucrose and iron carboxymaltose). In chronic inflammatory anemia, we use erythropoiesis-stimulating agents (erythropoietin alpha) and, in cases of mixed anemia, the combination of both treatments. The objective is always to reduce the need for perioperative transfusions and speed the recovery from postoperative anemia, as well as decrease the patient morbidity and mortality rate.

  14. Targeted disruption of the murine Facc gene: Towards the establishment of a mouse model for Fanconi anemia

    SciTech Connect

    Chen, M.; Auerbach, W.; Buchwald, M.

    1994-09-01

    Fanconi anemia (FA) is an autosomal recessive disease characterized by bone marrow failure, congenital malformations and predisposition to malignancies. The gene responsible for the defect in FA group C has been cloned and designated the Fanconi Anemia Complementation Group C gene (FACC). A murine cDNA for this gene (Facc) was also cloned. Here we report our progress in the establishment of a mouse model for FA. The mouse Facc cDNA was used as probe to screen a genomic library of mouse strain 129. More than twenty positive clones were isolated. Three of them were mapped and found to be overlapping clones, encompassing the genomic region from exon 8 to the end of the 3{prime} UTR of the mouse cDNA. A targeting vector was constructed using the most 5{prime} mouse genomic sequence available. The end result of the homologous recombination is that exon 8 is deleted and the neo gene is inserted. The last exon, exon 14, is essential for the complementing function of the FACC gene product; the disruption in the middle of the murine Facc gene should render this locus biologically inactive. This targeting vector was linearized and electroporated into R1 embryonic stem (ES) cells which were derived from the 129 mouse. Of 102 clones screened, 19 positive cell lines were identified. Four targeted cell lines have been used to produce chimeric mice. 129-derived ES cells were aggregated ex vivo into the morulas derived from CD1 mice and then implanted into foster mothers. 22 chimeras have been obtained. Moderately and strongly chimeric mice have been bred to test for germline transmission. Progeny with the expected coat color derived from 2 chimeras are currently being examined to confirm transmission of the targeted allele.

  15. The diagnosis of microcytic anemia by a rule-based expert system using VP-Expert.

    PubMed

    O'Connor, M L; McKinney, T

    1989-09-01

    We describe our experience in creating a rule-based expert system for the interpretation of microcytic anemia using the expert system development tool, VP-Expert, running on an IBM personal computer. VP-Expert processes data (complete blood cell count results, age, and sex) according to a set of user-written logic rules (our program) to reach conclusions as to the following causes of microcytic anemia: alpha- and beta-thalassemia trait, iron deficiency, and anemia of chronic disease. Our expert system was tested using previously interpreted complete blood cell count data. In most instances, there was good agreement between the expert system and its pathologist-author, but many discrepancies were found in the interpretation of anemia of chronic disease. We conclude that VP-Expert has a useful level of power and flexibility, yet is simple enough that individuals with modest programming experience can create their own expert systems. Limitations of such expert systems are discussed.

  16. Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease

    PubMed Central

    Hao, Jingcan; Wang, Wenyu; Wen, Yan; Xiao, Xiao; He, Awen; Wu, Cuiyan; Wang, Sen; Guo, Xiong; Zhang, Feng

    2017-01-01

    Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of growth and development failure of hand of KBD remains elusive now. In this study, we conducted a two-stage genome-wide association study (GWAS) of palmar length-width ratio (LWR) of KBD, totally including 493 study subjects. Affymetrix Genome Wide Human SNP Array 6.0 was applied for genome-wide SNP genotyping of 90 KBD patients. Association analysis was conducted by PLINK. Imputation analysis was performed by IMPUTE against the reference panel of the 1000 genome project. Two SNPs were selected for replication in an independent validation sample of 403 KBD patients. In the discovery GWAS, significant association was observed between palmar LWR and rs2071358 of COL2A1 gene (P value = 4.68 × 10−8). In addition, GWAS detected suggestive association signal at rs4760608 of COL2A1 gene (P value = 1.76 × 10−4). Imputation analysis of COL2A1 further identified 2 SNPs with association evidence for palmar LWR. Replication study observed significant association signals at both rs2071358 (P value = 0.017) and rs4760608 (P value = 0.002) of COL2A1 gene. Based on previous and our study results, we suggest that COL2A1 was a likely susceptibility gene involved in the hand development failure of KBD. PMID:28059113

  17. Evolution of New Disease Specificity at a Simple Resistance Locus in a Crop–Weed Complex: Reconstitution of the Lr21 Gene in Wheat

    PubMed Central

    Huang, Li; Brooks, Steven; Li, Wanlong; Fellers, John; Nelson, James C.; Gill, Bikram

    2009-01-01

    The wheat leaf-rust resistance gene Lr21 was first identified in an Iranian accession of goatgrass, Aegilops tauschii Coss., the D-genome donor of hexaploid bread wheat, and was introgressed into modern wheat cultivars by breeding. To elucidate the origin of the gene, we analyzed sequences of Lr21 and lr21 alleles from 24 wheat cultivars and 25 accessions of Ae. tauschii collected along the Caspian Sea in Iran and Azerbaijan. Three basic nonfunctional lr21 haplotypes, H1, H2, and H3, were identified. Lr21 was found to be a chimera of H1 and H2, which were found only in wheat. We attempted to reconstitute a functional Lr21 allele by crossing the cultivars Fielder (H1) and Wichita (H2). Rust inoculation of 5876 F2 progeny revealed a single resistant plant that proved to carry the H1H2 haplotype, a result attributed to intragenic recombination. These findings reflect how plants balance the penalty and the necessity of a resistance gene and suggest that plants can reuse “dead” alleles to generate new disease-resistance specificity, leading to a “death–recycle” model of plant-resistance gene evolution at simple loci. We suggest that selection pressure in crop–weed complexes contributes to this process. PMID:19364806

  18. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients

    PubMed Central

    Besarab, Anatole; Provenzano, Robert; Hertel, Joachim; Zabaneh, Raja; Klaus, Stephen J.; Lee, Tyson; Leong, Robert; Hemmerich, Stefan; Yu, Kin-Hung Peony; Neff, Thomas B.

    2015-01-01

    Background Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. This Phase 2a study tested efficacy (Hb response) and safety of roxadustat in anemic nondialysis-dependent chronic kidney disease (NDD-CKD) subjects. Methods NDD-CKD subjects with hemoglobin (Hb) ≤11.0 g/dL were sequentially enrolled into four dose cohorts and randomized to roxadustat or placebo two times weekly (BIW) or three times weekly (TIW) for 4 weeks, in an approximate roxadustat:placebo ratio of 3:1. Efficacy was assessed by (i) mean Hb change (ΔHb) from baseline (BL) and (ii) proportion of Hb responders (ΔHb ≥ 1.0 g/dL). Pharmacodynamic evaluation was performed in a subset of subjects. Safety was evaluated by adverse event frequency/severity. Results Of 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy. BL characteristics for roxadustat and placebo groups were comparable. In roxadustat-treated subjects, Hb levels increased from BL in a dose-related manner in the 0.7, 1.0, 1.5 and 2.0 mg/kg groups. Maximum ΔHb within the first 6 weeks was significantly higher in the 1.5 and 2.0 mg/kg groups than in the placebo subjects. Hb responder rates were dose dependent and ranged from 30% in the 0.7 mg/kg BIW group to 100% in the 2.0 mg/kg BIW and TIW groups versus 13% in placebo. Conclusions Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. Adverse events were similar in the roxadustat and placebo groups. Roxadustat produced dose-dependent increases in blood Hb among anemic NDD-CKD patients in a placebo-controlled trial. Clinical Trials Registration Clintrials.gov #NCT00761657. PMID:26238121

  19. [Hookworm discovered in a patient presenting with severe iron-deficiency anemia].

    PubMed

    Basset, D; Rullier, P; Segalas, F; Sasso, M

    2010-04-01

    The purpose of this report is to describe a case involving severe anemia in a patient from New Caledonia. Endoscopic discovery of adult hematophagic hookworms in mainland France is novel because it is exceptional. However, this case also reminds us that hookworm disease is extremely widespread in the world. It often goes unrecognized causing progressive, insidious anemia that can be severe though long-term tolerance is good.

  20. Incidence and risk factors of aplastic anemia in Latin American countries: the LATIN case-control study

    PubMed Central

    Maluf, Eliane; Hamerschlak, Nelson; Cavalcanti, Alexandre Biasi; Júnior, Álvaro Avezum; Eluf-Neto, José; Falcão, Roberto Passetto; Lorand-Metze, Irene G.; Goldenberg, Daniel; Santana, Cézar Leite; de Oliveira Werneck Rodrigues, Daniela; da Motta Passos, Leny Nascimento; Rosenfeld, Luis Gastão Mange; Pitta, Marimilia; Loggetto, Sandra; Feitosa Ribeiro, Andreza A.; Velloso, Elvira Deolinda; Kondo, Andrea Tiemi; de Miranda Coelho, Erika Oliveira; Pintão, Maria Carolina Tostes; de Souza, Hélio Moraes; Borbolla, José Rafael; Pasquini, Ricardo

    2009-01-01

    Background Associations between aplastic anemia and numerous drugs, pesticides and chemicals have been reported. However, at least 50% of the etiology of aplastic anemia remains unexplained. Design and Methods This was a case-control, multicenter, multinational study, designed to identify risk factors for agranulocytosis and aplastic anemia. The cases were patients with diagnosis of aplastic anemia confirmed through biopsy or bone marrow aspiration, selected through an active search of clinical laboratories, hematology clinics and medical records. The controls did not have either aplastic anemia or chronic diseases. A total of 224 patients with aplastic anemia were included in the study, each case was paired with four controls, according to sex, age group, and hospital where the case was first seen. Information was collected on demographic data, medical history, laboratory tests, medications, and other potential risk factors prior to diagnosis. Results The incidence of aplastic anemia was 1.6 cases per million per year. Higher rates of benzene exposure (≥30 exposures per year) were associated with a greater risk of aplastic anemia (odds ratio, OR: 4.2; 95% confidence interval, CI: 1.82–9.82). Individuals exposed to chloramphenicol in the previous year had an adjusted OR for aplastic anemia of 8.7 (CI: 0.87–87.93) and those exposed to azithromycin had an adjusted OR of 11.02 (CI 1.14–108.02). Conclusions The incidence of aplastic anemia in Latin America countries is low. Although the research study centers had a high coverage of health services, the underreporting of cases of aplastic anemia in selected regions can be discussed. Frequent exposure to benzene-based products increases the risk for aplastic anemia. Few associations with specific drugs were found, and it is likely that some of these were due to chance alone. PMID:19734415

  1. Sickle cell anemia and antisickling agents then and now.

    PubMed

    Mehanna, A S

    2001-02-01

    Sickle cell anemia is a genetic blood disorder arising from a point mutation in the beta-globin gene that leads to the replacement of glutamic acid residue by valine at the sixth position of the beta--chain of hemoglobin. At low oxygen tension, the mutant hemoglobin, sickle hemoglobin, polymerizes inside the red blood cells into a gel or further into fibers leading to a drastic decrease in the red cell deformability. As a result, micro-vascular occlusion arises which may lead to serious, sometimes fatal, crises. The present article reviews the historical, genetic, molecular, cellular, and clinical aspects of the disease. A review for the development and design of drugs to treat sickle cell anemia is presented. Anti-sickling agents are classified, based on the target to be modified, into three classes: the gene, the sickle hemoglobin molecule, and the red cell membrane modifiers. In spite of the full understanding of the pathology, physiology, and the molecular nature of the disease, and the development of large number of antisickling agents, a cure for sickle cell anemia still is unavailable. Strategies to treat sickle cell anemia since the early times of the disease state discovery in 1910, has focussed mainly on prophylactic measures to alleviate the painful crises. The article addresses clinical approaches used then and now to treat the disease, and the rationale of their use. Currently in clinical practice, hydroxyurea is the most commonly used agent to treat the disease, and it has been recently approved by the united states Food and Drug Administration as a drug for that purpose.

  2. Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response.

    PubMed

    Richardson, Chanté L; Delehanty, Lorrie L; Bullock, Grant C; Rival, Claudia M; Tung, Kenneth S; Kimpel, Donald L; Gardenghi, Sara; Rivella, Stefano; Goldfarb, Adam N

    2013-08-01

    The unique sensitivity of early red cell progenitors to iron deprivation, known as the erythroid iron restriction response, serves as a basis for human anemias globally. This response impairs erythropoietin-driven erythropoiesis and underlies erythropoietic repression in iron deficiency anemia. Mechanistically, the erythroid iron restriction response results from inactivation of aconitase enzymes and can be suppressed by providing the aconitase product isocitrate. Recent studies have implicated the erythroid iron restriction response in anemia of chronic disease and inflammation (ACDI), offering new therapeutic avenues for a major clinical problem; however, inflammatory signals may also directly repress erythropoiesis in ACDI. Here, we show that suppression of the erythroid iron restriction response by isocitrate administration corrected anemia and erythropoietic defects in rats with ACDI. In vitro studies demonstrated that erythroid repression by inflammatory signaling is potently modulated by the erythroid iron restriction response in a kinase-dependent pathway involving induction of the erythroid-inhibitory transcription factor PU.1. These results reveal the integration of iron and inflammatory inputs in a therapeutically tractable erythropoietic regulatory circuit.

  3. Inborn anemias in mice: (Annual report, 1982-1983)

    SciTech Connect

    Bernstein, S.E.

    1983-09-09

    The nature of the defects that shorten the effective lifespan of red blood cells in the circulation and which gave rise to anemia, jaundice and to spleen, liver and heart enlargement are studied because they so closely parallel inherited hemolytic anemias in man. In mice, ''hemolytic disease'' initiated by the ja, sph, sph/sup ha/, or the nb genes has been traced to abnormalities in the protein components of their red cell membranes. Polyacrylamide gel electrophoresis of detergent solubilized membranes reveal that in the different genetic types one or more of the major high molecular weight proteins called spectrins is decreased or totally missing. It is one thing to observe a correlation between missing or defective components in selected analytical procedures, and another to establish a causal relationship between the two. To investigate the possible interrelationships, we examined the associations between spectrin or ankyrin content, the severity of the resulting anemia, red cell osmotic fragilities, and the capacity of cells from each genotype to be deformed in a continuous osmotic gradient at constant sheer stress. Our findings indicate that sensitivity to osmotic stress, cell rigidity (inadequate deformability), deficiency of spectrin or ankyrin, and the severity of the anemia, are statistically highly correlated. 11 refs., 3 tabs.

  4. A mouse model for an erythropoietin-deficiency anemia.

    PubMed

    Zeigler, Brandon M; Vajdos, Janis; Qin, Wenning; Loverro, Linda; Niss, Knut

    2010-01-01

    In mammals, the production of red blood cells is tightly regulated by the growth factor erythropoietin (EPO). Mice lacking a functional Epo gene are embryonic lethal, and studying erythropoiesis in EPO-deficient adult animals has therefore been limited. In order to obtain a preclinical model for an EPO-deficient anemia, we developed a mouse in which Epo can be silenced by Cre recombinase. After induction of Cre activity, Epo(KO/flox) mice experience a significant reduction of serum EPO levels and consequently develop a chronic, normocytic and normochromic anemia. Furthermore, compared with wild-type mice, Epo expression in Epo(KO/flox) mice is dramatically reduced in the kidney, and expression of a well-known target gene of EPO signaling, Bcl2l1, is reduced in the bone marrow. These observations are similar to the clinical display of anemia in patients with chronic kidney disease. In addition, during stress-induced erythropoiesis these mice display the same recovery rate as their heterozygous counterparts. Taken together, these results demonstrate that this model can serve as a valuable preclinical model for the anemia of EPO deficiency, as well as a tool for the study of stress-induced erythropoiesis during limiting conditions of EPO.

  5. Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia.

    PubMed

    Friedrisch, João Ricardo; Cançado, Rodolfo Delfini

    2015-01-01

    Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15mg/kg; maximum of 1000mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia.

  6. Individualized treatment for iron deficiency anemia in adults

    PubMed Central

    Alleyne, Michael; Horne, McDonald K.; Miller, Jeffery L.

    2008-01-01

    Iron deficiency is one of the most common disorders affecting mankind, and iron deficiency anemia continues to represent a major public health problem worldwide. It is especially common among women of childbearing age due to pregnancy and menstrual blood loss. Additional patient groups include those with other sources of blood loss, malnutrition or gut malabsorption. Iron deficiency anemia remains quite prevalent despite the widespread ability to diagnose the disease and availability of medicinal iron preparations. Therefore, new approaches are needed to effectively manage these patient populations. In this review, the diagnosis and treatment of iron deficiency anemia are discussed with emphasis placed upon consideration of patient specific features. It is proposed that all patients participate in their own care by helping their physician to identify a tolerable daily iron dose, formulation, and schedule. Dosing cycles are recommended for iron replacement based upon the tolerated daily dose and the total iron deficit. Each cycle consists of 5000mg of oral elemental iron ingested over at least one month with appropriate follow-up. This approach should assist physicians and their patients with the implementation of individualized treatment strategies for patients with iron deficiency anemia. PMID:18954837

  7. Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia

    PubMed Central

    Friedrisch, João Ricardo; Cançado, Rodolfo Delfini

    2015-01-01

    Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15 mg/kg; maximum of 1000 mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia. PMID:26670403

  8. Anemia and iron deficiency in gastrointestinal and liver conditions

    PubMed Central

    Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

    2016-01-01

    Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice. PMID:27672287

  9. Determinants of Anemia and Hemoglobin Concentration in Haitian School-Aged Children

    PubMed Central

    Iannotti, Lora L.; Delnatus, Jacques R.; Odom, Audrey R.; Eaton, Jacob C.; Griggs, Jennifer J.; Brown, Sarah; Wolff, Patricia B.

    2015-01-01

    Anemia diminishes oxygen transport in the body, resulting in potentially irreversible growth and developmental consequences for children. Limited evidence for determinants of anemia exists for school-aged children. We conducted a cluster randomized controlled trial in Haiti from 2012 to 2013 to test the efficacy of a fortified school snack. Children (N = 1,047) aged 3–13 years were followed longitudinally at three time points for hemoglobin (Hb) concentrations, anthropometry, and bioelectrical impedance measures. Dietary intakes, infectious disease morbidities, and socioeconomic and demographic factors were collected at baseline and endline. Longitudinal regression modeling with generalized least squares and logit models with random effects identified anemia risk factors beyond the intervention effect. At baseline, 70.6% of children were anemic and 2.6% were severely anemic. Stunting increased the odds of developing anemia (adjusted odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.05–2.08) and severe anemia (adjusted OR: 2.47, 95% CI: 1.30–4.71). Parent-reported vitamin A supplementation and deworming were positively associated with Hb concentrations, whereas fever and poultry ownership showed a negative relationship with Hb concentration and increased odds of severe anemia, respectively. Further research should explore the full spectrum of anemia etiologies in school children, including genetic causes. PMID:26350448

  10. Prevalence of Iron deficiency anemia in children with liver cirrhosis: A cross-sectional study

    PubMed Central

    Zareifar, Soheila; Dehghani, Seyed Mohsen; Rahanjam, Najmeh; Farahmand Far, Mohammad Reza

    2015-01-01

    Background: Among the many complications reported for cirrhosis, iron deficiency anemia (IDA) has attracted much attention. This type of anemia, in contrast to other types of anemia, is easy to treat prophylactically, but if left untreated can lead to a poor quality of life. The aim of this study was to estimate the hemoglobin and serum iron levels among patients with liver cirrhosis for the early diagnosis of IDA and to avoid unnecessary testing and iron supplementation. Subjects and Methods: In this cross-sectional study, 88 children diagnosed with cirrhosis were included, and the values of hemoglobin, serum iron levels and relationship between serum iron (SI), total iron-binding capacity (TIBC), prothrombine time (PT), international normalization ratio (INR), total and direct bilirubin and hepatic enzymes were estimated using paired t test, Mann-Whitney, Chi-square and Kruskal-Wallis tests. Results: Forty-six (52.3%) of 88 children were girls and 42 (47.7%) were boys. Forty-eight (54.5%) patients had anemia and 8 (9%) had iron deficiency anemia (5 boys, 5.6%, and 3 girls, 3.4%). No relationships were observed between iron deficiency anemia and the patient’s age or gender, whereas there was a relationship between iron deficiency and severity and duration of the disease, although the correlation was not statistically significant. Conclusion: The high frequency of iron deficiency anemia in children with cirrhosis (9%) suggests that timely screening should be used for early diagnosis and treatment. PMID:26261697

  11. Aplastic anemia associated to systemic lupus erythematosus in an AIDS patient: a case report.

    PubMed

    de Oliveira, Leonardo Rodrigues; Ferreira, Thaís Camargos; Neves, Fernando de Freitas; Meneses, Antônio Carlos de Oliveira

    2013-01-01

    Aplastic anemia is a bone marrow failure syndrome characterized by peripheral cytopenias and hypocellular bone marrow. Although aplastic anemia is idiopathic in most cases, rheumatic diseases such as systemic lupus erythematosus are recognized as causes of aplastic anemia, with their possible etiological mechanisms being T and B lymphocyte dysfunction and pro-inflammatory cytokines and autoantibody production directed against bone marrow components. In the course of the human immunodeficiency virus infection/acquired immunodeficiency syndrome, the identification of autoantibodies and the occurrence of rheumatic events, in addition to the natural course of systemic lupus erythematosus which is modified by immune changes that are characteristic of human immunodeficiency virus infection/acquired immunodeficiency syndrome, make the diagnosis of systemic lupus erythematosus challenging. This study reports the case of a woman with acquired immunodeficiency syndrome treated with a highly active antiretroviral therapy, who had prolonged cytopenias and hypocellular bone marrow consistent with aplastic anemia. The clinical picture, high autoantibodies titers, and sustained remission of the patient's hematological status through immunosuppression supported the diagnosis of systemic lupus erythematosus-associated aplastic anemia. This is the first report of aplastic anemia concurrent with systemic lupus erythematosus and acquired immunodeficiency syndrome, providing additional evidence that immune dysfunction is a key part of the pathophysiological mechanism of aplastic anemia.

  12. Molecular Mechanisms of Hepcidin Regulation: Implications for the Anemia of CKD

    PubMed Central

    Babitt, Jodie L.; Lin, Herbert Y.

    2010-01-01

    Anemia is prevalent in patients with chronic kidney disease (CKD) and is associated with a lower quality of life and a higher risk of adverse outcomes including cardiovascular disease and death. Anemia management in CKD patients currently revolves around the use of erythropoiesis-stimulating agents (ESAs) and supplemental iron. However, many patients do not respond adequately and/or require high doses of these medications. Furthermore, recent clinical trials have shown that targeting higher hemoglobin levels with conventional therapies leads to increased cardiovascular morbidity and mortality, particularly when higher doses of ESAs are used, and in patients who are poorly responsive to therapy. One explanation for the poor response to conventional therapies in some patients is that these treatments do not fully address the underlying cause of the anemia. In many CKD patients, like patients with other chronic inflammatory diseases, poor absorption of dietary iron and inability to utilize the body's iron stores contributes to the anemia. Recent research suggests that these abnormalities in iron balance may be caused by elevated levels of the key iron regulatory hormone hepcidin. This article reviews the pathogenesis of anemia in CKD, the role and regulation of hepcidin in systemic iron homeostasis and the anemia of CKD, and the potential diagnostic and therapeutic implications of these findings. PMID:20189278

  13. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    ClinicalTrials.gov

    2017-03-21

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  14. Epidemiology of anemia in older adults.

    PubMed

    Patel, Kushang V

    2008-10-01

    Anemia is a common, multifactorial condition among older adults. The World Health Organization (WHO) definition of anemia (hemoglobin concentration <12 g/dL in women and <13 g/dL in men) is most often used in epidemiologic studies of older adults. More than 10% of community-dwelling adults age 65 years and older has WHO-defined anemia. After age 50 years, prevalence of anemia increases with advancing age and exceeds 20% in those 85 years and older. In nursing homes, anemia is present in 48% to 63% of residents. Incidence of anemia in older adults is not well characterized. Among older adults with anemia, approximately one third have evidence of iron, folate, and/or vitamin B(12) deficiency, another third have renal insufficiency and/or chronic inflammation, and the remaining third have anemia that is unexplained. Several studies demonstrate that anemia is associated with poorer survival in older adults. This review details the distribution and consequences of anemia in older adults and identifies future epidemiologic research needs.

  15. Assessing Chaos in Sickle Cell Anemia Crises

    NASA Astrophysics Data System (ADS)

    Harris, Wesley; Le Floch, Francois

    2006-11-01

    Recent developments in sickle cell research and blood flow modeling allow for new interpretations of the sickle cell crises. With an appropriate set of theoretical and empirical equations describing the dynamics of the red cells in their environment, and the response of the capillaries to major changes in the rheology, a complete mathematical system has been derived. This system of equations is believed to be of major importance to provide new and significant insight into the causes of the disease and related crises. With simulations, it has been proven that the system transition from a periodic solution to a chaotic one, which illustrates the onset of crises from a regular blood flow synchronized with the heart beat. Moreover, the analysis of the effects of various physiological parameters exposes the potential to control chaotic solutions, which, in turn, could lead to the creation of new and more effective treatments for sickle cell anemia. .

  16. Current Management of Sickle Cell Anemia

    PubMed Central

    McGann, Patrick T.; Nero, Alecia C.; Ware, Russell E.

    2013-01-01

    Proper management of sickle cell anemia (SCA) begins with establishing the correct diagnosis early in life, ideally during the newborn period. The identification of affected infants by neonatal screening programs allows early initiation of prophylactic penicillin and pneumococcal immunizations, which help prevent overwhelming sepsis. Ongoing education of families promotes the early recognition of disease-released complications, which allows prompt and appropriate medical evaluation and therapeutic intervention. Periodic evaluation by trained specialists helps provide comprehensive care, including transcranial Doppler examinations to identify children at risk for primary stroke, plus assessments for other parenchymal organ damage as patients become teens and adults. Treatment approaches that previously highlighted acute vaso-occlusive events are now evolving to the concept of preventive therapy. Liberalized use of blood transfusions and early consideration of hydroxyurea treatment represent a new treatment paradigm for SCA management. PMID:23709685

  17. Sickle cell anemia from central India: a retrospective analysis.

    PubMed

    Jain, Dipty; Italia, Khushnooma; Sarathi, Vijaya; Ghoshand, Kanjaksha; Colah, Roshan

    2012-11-01

    Although sickle cell anemia in India is believed to have a mild clinical presentation, few studies report severe disease in many patients from central India. Hence, we have retrospectively studied 316 children with SCA who were followed up for a period of 5.8±5.7 years. There were 55.4 blood transfusions, 43.3 episodes of vaso-occlusive crises requiring hospitalization, and 108.9 hospitalizations per 100 person years. Ninety six (30%) patients had severe disease whereas 74 patients also fulfilled the criteria for hydroxyurea therapy. Significant proportion of children with sickle cell anemia from central India present with severe clinical presentation and require regular medical attention.

  18. [Anemia in peritoneal dialysis patients].

    PubMed

    Lausević, Mirjana; Nesić, Vidosava; Jovanović, Natasa; Stojimirović, Biljana

    2006-01-01

    A normocytic normochromic anemia is one of the first signs of renal failure. Since anemia increases morbidity and mortality, its elimination is one of the essential objectives of the treatment. Human recombinant erythropoietin (rHuEPO) has changed the therapeutical approach to anemia. The aim of the present study was to compare efficacy of anemia correction in peritoneal dialysis patients depending on treatment and dialysis modality. The study is the retrospective analysis of 64 patients who presented to our Clinic in 2003. Eighteen (28.13%) patients were treated with rHuEPO, 14 (28%) underwent continuous ambulatory peritoneal dialysis (CAPD), 2 (100%)--automated peritoneal dialysis (APD) and 2 (33.3%)--intermittent peritoneal dialysis (IPD). Mean hemoglobin level was 98.6 +/- 17.82 g/l in patients treated with rHuEPO versus 98.81 +/- 15.14 g/l in patients without rHuEPO treatment. Erythropoietin requirements were 3392.85 +/- 1211.77 IU/week All patients received iron supplementation during rHuEPO therapy. Mean serum ferritin levels were 463.41 +/- 360 ug/l. Transferrin saturation (TSAT) was 0.35 +/- 0.16%. No difference of serum iron and TSAT levels was found between CAPD and IPD patients. The degree of anemia significantly differed between CAPD and IPD patients. A total of 17.11% of PD patients were given blood transfusions, most frequently during the first three months after the onset of dialysis. Our conclusion is that the number of patients receiving rHuEPO should be increased, as 50% of our patients should be substituted, while only 28% are being treated. As 50% of patients receiving rHuEPO failed to reach target Hgb levels, higher EPO doses should be considered. Iron stores should be continuously monitored, particularly in patients receiving rHuEPO, since iron deficiency is an important problem for patients undergoing peritoneal dialysis, especially during erythropoietin therapy. Oral iron supplementation is satisfactory in the majority of patients, and iron

  19. A new locus for X-linked dominant Charcot–Marie–Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene

    PubMed Central

    Kennerson, Marina L.; Yiu, Eppie M.; Chuang, David T.; Kidambi, Aditi; Tso, Shih-Chia; Ly, Carolyn; Chaudhry, Rabia; Drew, Alexander P.; Rance, Gary; Delatycki, Martin B.; Züchner, Stephan; Ryan, Monique M.; Nicholson, Garth A.

    2013-01-01

    Hereditary motor and sensory disorders of the peripheral nerve form one of the most common groups of human genetic diseases collectively called Charcot–Marie–Tooth (CMT) neuropathy. Using linkage analysis in a three generation kindred, we have mapped a new locus for X-linked dominant CMT to chromosome Xp22.11. A microsatellite scan of the X chromosome established significant linkage to several markers including DXS993 (Zmax = 3.16; θ = 0.05). Extended haplotype analysis refined the linkage region to a 1.43-Mb interval flanked by markers DXS7110 and DXS8027. Whole exome sequencing identified a missense mutation c.G473A (p.R158H) in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene. The change localized within the 1.43-Mb linkage interval, segregated with the affected phenotype and was excluded in ethnically matched control chromosomes. PDK3 is one of the four isoenzymes regulating the pyruvate dehydrogenase complex (PDC), by reversible phosphorylation, and is a nuclear-coded protein located in the mitochondrial matrix. PDC catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA and is a key enzyme linking glycolysis to the energy-producing Krebs cycle and lipogenic pathways. We found that the R158H mutation confers enzyme hyperactivity and binds with stronger affinity than the wild-type to the inner-lipoyl (L2) domain of the E2p chain of PDC. Our findings suggest a reduced pyruvate flux due to R158H mutant PDK3-mediated hyper-phosphorylation of the PDC as the underlying pathogenic cause of peripheral neuropathy. The results highlight an important causative link between peripheral nerve degeneration and an essential bioenergetic or biosynthetic pathway required for the maintenance of peripheral nerves. PMID:23297365

  20. Retroviral transfer of a human beta-globin/delta-globin hybrid gene linked to beta locus control region hypersensitive site 2 aimed at the gene therapy of sickle cell disease.

    PubMed Central

    Takekoshi, K J; Oh, Y H; Westerman, K W; London, I M; Leboulch, P

    1995-01-01

    Human gamma-globin and delta-globin chains have been previously identified as strong inhibitors of the polymerization of hemoglobin S, in contrast to the beta-globin chain, which exerts only a moderate antisickling effect. However, gamma-globin and delta-globin are normally expressed at very low levels in adult erythroid cells, in contrast to beta-globin. We report the design of a beta-globin/delta-globin hybrid gene, beta/delta-sickle cell inhibitor 1 (beta/delta-SCI1) and its transduction by retrovirus-mediated gene transfer. The beta/delta-SCI1-encoding gene retains the overall structure of the human beta-globin gene, while incorporating specific amino acid residues from the delta chain previously found responsible for its enhanced antisickling properties. To achieve high expression levels of beta/delta-SCI1 in adult erythrocytes, the hybrid gene was placed under the transcriptional control of the human beta-globin promoter and the DNase I hypersensitive site 2 of the human beta locus control region. High-titer retroviruses were generated, and stable proviral transmission was achieved in infected cells. The mRNA expression levels of the beta/delta-SCI1 gene in infected, dimethyl sulfoxide-induced murine erythroleukemia cells approached 85% of the endogenous murine beta maj-globin mRNA, on a per gene basis, evidence that high gene expression levels were achieved in adult erythroid cells. Further evaluation of this strategy in transgenic animal models of sickle cell disease should assess its efficacy for the gene therapy of human patients. Images Fig. 4 Fig. 5 PMID:7708766